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Archive for the ‘Cell Medicine’ Category

Duke Stem Cell and Regenerative Medicine Program

Thursday, August 4th, 2016

PLEASE NOTE: In early 2016, the Duke Stem Cell and Regenerative Medicine Program will be incorporated into a new Initiative called Regeneration Next. Please follow this link for information and stay tuned for our Launch. Overview Our program brings together basic scientists and clinicians studying stem cells in a variety of adult and developing organ systems. The goal is to understand and exploit their remarkable capacity to maintain healthy tissues and to replace cells lost by disease or injury. Program highlights include:

Executive Director Search The new tissueregenerationinitiative at Duke is hiring an Executive Director to work closely with the Director, Co-Directors, and faculty members to promote and integrate discovery research, training, and applications in the broad field of tissue regeneration.Applications from candidates who have a Ph.D. and postdoctoral research experience in the relevant areas of developmental biology, stem cell biology, or tissue regeneration are of particular interest. Please submit a cover letter, curriculum vitae, summary of research accomplishments and any administrative leadership experience, and a list of at least three references to Academic Jobs Online. Questions may be directed to .

Niche regulation of new neurons production in the adult brain Robust production of new neurons continues in the adult rodent brain, but how this is sustained remains unknown. Researchers in Dr. Chay T. Kuos laboratory found that self-assembly of radial glia into support structures for adult stem cells is critical for continued neurogenesis. More...

Zebrafish heart regeneration During heart regeneration in zebrafish, retinoic production in endocardial and epicardial cells localizes to areas of tissue damage, where it promotes cardiomyocyte proliferation. More...

Intestinal Crypt Proliferation Stem cell/transit amplifying compartments (green) reside in the base of each mouse intestinal crypt. These cells give rise to the multiple lineages of the intestinal epithelium (Lechler lab). More...

Lung epithelial stem cell regulationThe airways of the lung are lined by an epithelium that contains large numbers of cells specialized for making and secreting glycoproteins and mucus, as well as multiciliated cells that remove the mucus and the particles trapped in it. More...

Role of immune cells in the spermatogonial stem cell niche In addition to their roles in immune and inflammatory responses, macrophages have diverse functions in development. In reproductive biology, macrophages have been implicated in ovarian follicular growth and in Leydig cell function, but their role in spermatogonial differentiation has not been examined. More...

Drosophila hindgut repairThe fruit fly Drosophila has long been a leading genetic model for stem cell research. However, until recently no Drosophila models existed for study of mechanisms by which adult organs lacking active stem cells repair damaged tissue. More...

Indispensible pre-mitotic endocycles promote aneuploidy in the Drosophila rectum

Time lapse imaging of a tripolar division during developmental organ regeneration in the Drosophila hindgut. These divisions occur in cells with extra copies of the genome (polyploid cells) and produce an adult organ in which many of the cells have variable, imbalanced chromosome numbers (aneuploid cells). DNA is in purple, and centrosomes and cell membranes are in green.

Fox Lab. Schoenfelder et al. (2014) Development 141:3551-3560

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Duke Stem Cell and Regenerative Medicine Program

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13th Stem Cell Research & Regenerative Medicine Overview

Thursday, August 4th, 2016

Dear Colleague,

We welcome you to GTCbio's 13th Stem Cell Research & Regenerative Medicine Conference, to be held on April 25-26, 2016 in Boston, MA. This conference presents information regarding cutting-edge developments in all areas of stem cell research, including the biology, medicine, applications and regulations of stem cells. Topics of discussion include recent developments in pre-clinical and clinical trials of stem cell therapy, regenerative medicine and tissue engineering, cancer stem cells, immunotherapy, stem cell reprogramming, and regulatory policies regarding stem cell research.

Conference 1: 13th Stem Cell Research & Regenerative Medicine

I. Cells for Therapeutic Development, Disease Modeling, & Drug Discovery II. Advances in Adult & Pluripotent Stem Cell Research & Technology III. Frontiers in Tissue Engineering IV. Immunotherapy - Revolution in Disease Treatments V. Joint Plenary Session: Translation to the Clinic: What's in the Pipeline? VI. Joint Plenary Session: Regulatory Challenges in Cell Therapy

This conference is part of our larger Stem Cell Summit 2016, which includes two back-to-back conferences including joint sessions:

Conference 1: 13th Stem Cell Research & Regenerative Medicine Conference 2: 5th Stem Cell Product Development & Commercialization

Sign up for the Summit to have access to both conferences!

We hope to see you there!

Best regards,

The 2016 Advisory Committee

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13th Stem Cell Research & Regenerative Medicine Overview

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Reviews – Cell Therapy News

Thursday, August 4th, 2016

Stem and Progenitor Cell-Based Therapy of the Central Nervous System: Hopes, Hype, and Wishful Thinking Goldman, SA Cell Stem Cell 2016-02-04 17.05 | Feb 8 Mesenchymal Stromal Cells in Renal Transplantation: Opportunities and Challenges Casiraghi, F; Perico, N; Cortinovis, M; Remuzzi, G Nat Rev Nephrol 2016-02-08 17.05 | Feb 8 Manufacturing of AcMNPV Baculovirus Vectors to Enable Gene Therapy Trials Kwang, TW; Zeng, X; Wang, S Mol Ther Methods Clin Dev 2016-01-27 17.04 | Feb 1 Targeted Approaches to Induce Immune Tolerance for Pompe Disease Therapy Doerfler, PA; Nayak, S; Corti, M; Morel, L; Herzog, RW; Byrne, BJ Mol Ther Methods Clin Dev 2016-01-27 17.04 | Feb 1 Hurdles to the Introduction of New Therapies for Immune-Mediated Kidney Diseases Anders, HJ; Jayne, DRW; Rovin, BH Nat Rev Immunol 2016-01-25 17.03 | Jan 25 Megakaryocyte and Megakaryocyte Precursor Related Gene Therapies Wilcox, DA Blood 2016-01-19 17.03 | Jan 25 Gene Therapy Approaches against Cancer Using In Vivo and Ex Vivo Gene Transfer of Interleukin-12 Hernandez-Alcoceba, R; Poutou, J; Ballesteros-Briones, MC; Smerdou, C Immunotherapy 2016/01/20 17.03 | Jan 25 Biology and Applications of CRISPR Systems: Harnessing Natures Toolbox for Genome Engineering Wright, AV; Nunez, JK; Doudna, JA Cell 2016-01-14 17.02 | Jan 18 Genome Editing Technologies for Gene and Cell Therapy Maeder, ML; Gersbach, CA Mol Ther 2016-01-12 17.02 | Jan 18 Deciphering CD137 (4-1bb) Signaling in T-Cell Costimulation for Translation into Successful Cancer Immunotherapy Sanchez-Paulete, AR; Labiano, S; Rodriguez-Ruiz, ME; Azpilikueta, A; Etxeberria, I; Bolaos, E; Lang, V; Rodriguez, M; Aznar, MA; Jure-Kunkel, M; Melero, I Eur J Immunol 2016-01-15 17.02 | Jan 18 Current Status of Treating Neurodegenerative Disease with Induced Pluripotent Stem Cells Pen, AE; Jensen, UB Acta Neurol Scand 2016-01-08 17.01 | Dec 11 Allogeneic Stem Cell Transplantation for Multiple Myeloma: Is There a Future? Dhakal, B; Vesole, DH; Hari, PN Bone Marrow Transplant 2016-01-04 17.01 | Dec 11 Stem Cell-Based Therapies to Promote Angiogenesis in Ischemic Cardiovascular Disease Hou, L; Kim, JJ; Woo, YJ; Huang, NF Am J Physiol Heart Circ Physiol 2015-12-18 17.00 | Jan 4 Allogeneic Stem Cell Transplantation for Multiple Myeloma: Is There a Future? Dhakal, B; Vesole, DH; Hari, PN Bone Marrow Transplant 2016-01-04 17.00 | Jan 4 Preclinical Modeling of Hematopoietic Stem Cell Transplantation: Advantages and Limitations Stolfi, JL; Pai, CS; Murphy, WJ FEBS J 2015-12-07 16.46 | Dec 14 Strategies for Improving the Efficacy of Donor Lymphocyte Infusion following Stem Cell Transplantation Stamouli, M; Gkirkas, K; Tsirigotis, P Immunotherapy 2015-12-07 16.46 | Dec 14 Interneuron Transplantation as a Treatment for Epilepsy Hunt, RF; Baraban, SC Cold Spring Harb Perspect Med 2015-12-01 16.45 | Dec 7 Humanized Mouse Models for Transplant Immunology Kenney, LL; Shultz, LD; Greiner, DL; Brehm, MA Am J Transplant 2015-11-20 16.44 | Nov 30 Gene Therapy for Cancer: Regulatory Considerations for Approval Husain, SR; Han, J; Au, P; Shannon, K; Puri, RK Cancer Gene Ther 2015-11-20 16.43 | Nov 23 New Approaches to Biological Pacemakers: Links to Sinoatrial Node Development Vedantham, V Trends Mol Med 2015-11-19 16.43 | Nov 23 Inflammation in Tissue Engineering: The Janus between Engraftment and Rejection Annunziata, C; Alessandra, C; Attila, T; Susanne, M; Teodori, L Eur J Immunol 2015-11-12 16.42 | Nov 16 Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma: Stem Cell Transplantation Methods that Enhance Stemness Tobita, M; Tajima, S; Mizuno, H Stem Cell Res Ther 2015-11-05 16.41 | Nov 9 Novel Immunotherapies in Lymphoid Malignancies Batlevi, CL; Renier, EM; Brentjens, RJ; Younes, A Nat Rev Clin Oncol 2015-11-03 16.41 | Nov 9 Skeletal Stem Cells and Their Contribution to Skeletal Fragility: Senescence and Rejuvenation Aldahmash, A Biogerontology 2015-10-28 16.40 | Nov 2 CRISPR/Cas9: Molecular Tool for Gene Therapy to Target Genome and Epigenome in the Treatment of Lung Cancer Sachdeva, M; Sachdeva, N; Pal, M; Gupta, N; Khan, IA; Majumdar, M; Tiwari, A Cancer Gene Ther 2015/10/23 16.39 | Oct 26 Gene Therapy Returns to Center Stage Naldini, L Nature 2015/10/14 16.38 | Oct 19 Stem Cell Microenvironment on a Chip: Current Technologies for Tissue Engineering and Stem Cell Biology Park, D; Lim, J; Park, JY; Lee, SH Stem Cells Transl Med 2015-10-08 16.38 | Oct 19 Improving Cell-Based Therapies by Nanomodification Chen, W; Fu, L; Chen, X J Control Release 2015-09-27 16.37 | Oct 5 Potential of GABA-ergic Cell Therapy for Schizophrenia, Neuropathic Pain, and Alzheimers and Parkinsons Diseases Shetty, AK; Bates, A Brain Res 2015-09-27 16.37 | Oct 5 Engineering Cell Fate for Tissue Regeneration by In Vivo Transdifferentiation de Lzaro, I; Kostarelos, K Stem Cell Rev 2015-09-24 16.36 | Sep 28 siRNA Versus miRNA as Therapeutics for Gene Silencing Lam, JKW; Chow, MYT; Zhang, Y; Leung, SWS Mol Ther Nucleic Acids 2015-09-15 16.35 | Sep 21 Cellular Engineering and Therapy in Combination with Cord Blood Allografting in Pediatric Recipients Cairo, MS; Tarek, N; Lee, DA; Delaney, C Bone Marrow Transplant 2015-09-14 16.35 | Sep 21 Lentivirus Technologies for Modulation of the Immune System Houghton, BC; Booth, C; Thrasher, AJ Curr Opin Pharmacol 2015-09-10 16.34 | Sep 14 Cancer Gene Therapy with T Cell Receptors and Chimeric Antigen Receptors Stauss, HJ; Morris, EC; Abken, H Curr Opin Pharmacol 2015-09-04 16.34 | Sep 14 Alphavirus Vectors as Tools in Neuroscience and Gene Therapy Lundstrom, K Virus Res 2015-08-22 16.33 | Aug 31 Virus-Specific T Cell Therapy in Solid Organ Transplantation Roemhild, A; Reinke, P Transpl Int 2015-08-18 16.32 | Aug 24 Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering Shamloo, A; Mohammadaliha, N; Mohseni, M J Biotechnol 2015-08-14 16.32 | Aug 24 Controlled Release Strategies for Modulating Immune Responses to Promote Tissue Regeneration Dumont, CM; Park, J; Shea, LD J Control Release 2015-08-08 16.31 | Aug 17 Coming to TERMs with Tissue Engineering and Regenerative Medicine in the Lung Prakash, YS; Tschumperlin, DJ; Stenmark, KR Am J Physiol Lung Cell Mol Physiol 2015-08-07 16.31 | Aug 17 Preventing Stem Cell Transplantation-Associated Viral Infections Using T-Cell Therapy Tzannou, I; Leen, AM Immunotherapy 2015-08-07 16.31 | Aug 17 Advanced Imaging Approaches for Regenerative Medicine: Emerging Technologies for Monitoring Stem Cell Fate In Vitro and In Vivo Kupfer, ME; Ogle, BM Biotechnol J 2015-07-30 16.30 | Aug 10 Cell Therapy for Parkinson S Disease: Functional Role of the Host Immune Response on Survival and Differentiation of Dopaminergic Neuroblasts Wenker, SD; Celeste, Leal, M; Isabel, Farias, M; Zeng, X; Pitossi, FJ Brain Res 2015-07-31 16.30 | Aug 10 Adoptive T-Cell Therapy for Cancer: The Era of Engineered T Cells Bonini, C; Mondino, A Eur J Immunol 2015-07-22 16.29 | Jul 27 Prospects of Neurotrophic Factors for Parkinsons Disease: Comparison of Protein and Gene Therapy Domanskyi, A; Saarma, M; Airavaara, M Hum Gene Ther 2015-07-15 16.28 | Jul 20 Modified mRNA as an Alternative to Plasmid DNA (pDNA) for Transcript Replacement and Vaccination Therapy Youn, H; Chung, JK Expert Opin Biol Ther 2015-06-30 16.27 | Jul 13 Scaffolds and Tissue Regeneration: An Overview of the Functional Properties of Selected Organic Tissues Rebelo, MA; Alves, TF; de, Lima, R; Oliveira, JM, Jr; Vila, MM; Balcao, VM; Severino, P; Chaud, MV J Biomed Mater Res B Appl Biomater 2015-07-07 16.27 | Jul 13 Recent Therapeutic Approaches for Spinal Cord Injury Raspa, A; Pugliese, R; Maleki, M; Gelain, F Biotechnol Bioeng 2015-07-01 16.26 | Jul 6 IL-12 and IL-23 Cytokines: From Discovery to Targeted Therapies for Immune-Mediated Inflammatory Diseases Teng, MWL; Bowman, EP; McElwee, JJ; Smyth, MJ; Casanova, JL; Cooper, AM; Cua, DJ Nat Med 2015-06-29 16.25 | Jun 29 Mesenchymal Stromal Cells and Hematopoietic Stem Cell Transplantation Bernardo, ME; Fibbe, WE Immunol Lett 2015-06-24 16.25 | Jun 29 Cell Therapy in Muscular Dystrophies: Many Promises in Mice and Dogs, Few Facts in Patients Skuk, D; Tremblay, JP Expert Opin Biol Ther 2015-06-16 16.24 | Jun 22 Cell Therapy for Immunosuppression after Kidney Transplantation Morath, C; Schmitt, A; Zeier, M; Schmitt, M; Sandra-Petrescu, F; Opelz, G; Terness, P; Schaier, M; Kleist, C Langenbecks Arch Surg 2015-06-17 16.24 | Jun 22 Epithelial-Mesenchymal Interactions in Urinary Bladder and Small Intestine and How to Apply Them in Tissue Engineering Jerman, UD; Kreft, ME; Veranic, P Tissue Eng Part B Rev 2015-06-12 16.23 | Jun 15 Advancement of the Subchondral Bone Plate in Translational Models of Osteochondral Repair Implications for Tissue Engineering Approaches Orth, P; Madry, H Tissue Eng Part B Rev 2015-06-12 16.23 | Jun 15 T-Cell and Natural Killer Cell Therapies for Hematologic Malignancies after Hematopoietic Stem Cell Transplantation: Enhancing The Graft-versus-Leukemia Effect Cruz, CR; Bollard, CM Haematologica 2015-06-02 15.22 | Jun 8 Overview of Hydrogel-Based Strategies for Application in Cardiac Tissue Regeneration Sun, X; Nunes, SS Biomed Mater 2015-06-04 15.22 | Jun 8 RNA Interference Approaches for Treatment of HIV-1 Infection Bobbin, ML; Burnett, JC; Rossi, JJ Genome Med 2015-05-28 16.21 | Jun 1 Two-Photon Polymerization Microfabrication of Hydrogels: An Advanced 3D Printing Technology for Tissue Engineering and Drug Delivery Xing, JF; Zheng, ML; Duan, XM Chem Soc Rev 2015-05-20 16.20 | May 25 Spinal Muscular Atrophy-Recent Therapeutic Advances for an Old Challenge Faravelli, I; Nizzardo, M; Comi, GP; Corti, S Nat Rev Neurol 2015-05-19 16.20 | May 25 Autologous, Allogeneic, Induced Pluripotent Stem Cell or a Combination Stem Cell Therapy? Where Are We Headed in Cartilage Repair and Why Vonk, LA; de, Windt, TS; Slaper-Cortenbach, IC; Saris, DB Stem Cell Res Ther 2015-05-15 16.19 | May 18 Neurogenetics and Gene Therapy for Reward Deficiency Syndrome: Are We Going to the Promised Land? Blum, K; Thanos, PK; Badgaiyan, RD; Febo, M; Oscar-Berman, M; Fratantonio, J; Demotrovics, Z; Gold, MS Expert Opin Biol Ther 2015-05-14 16.19 | May 18 Immune-Related Strategies Driving Immunotherapy in Breast Cancer Treatment: A Real Clinical Opportunity Ravelli, A; Reuben, JM; Lanza, F; Anfossi, S; Cappelletti, MR; Zanotti, L; Gobbi, A; Milani, M; Spada, D; Pedrazzoli, P; Martino, M; Bottini, A; Generali, D Expert Rev Anticancer Ther 2015-04-30 16.18 | May 11 Mesenchymal Stromal Cell Therapy in Hematology: From Laboratory to Clinic and Back Again De, Becker, A; Van, Riet, I Stem Cells Dev 2015-04-29 16.17 | May 4 Immune-Related Strategies Driving Immunotherapy in Breast Cancer Treatment: A Real Clinical Opportunity Ravelli, A; Reuben, JM; Lanza, F; Anfossi, S; Cappelletti, MR; Zanotti, L; Gobbi, A; Milani, M; Spada, D; Pedrazzoli, P; Martino, M; Bottini, A; Generali, D Expert Rev Anticancer Ther 2015-04-30 16.17 | May 4 The Endometrium as a Source of Mesenchymal Stem Cells for Regenerative Medicine Mutlu, L; Hufnagel, D; Taylor, HS Biol Reprod 2015-04-22 16.16 | Apr 27 Dental Stem Cells in Pulp Regeneration: Near Future or Long Road Ahead? Hilkens, P; Meschi, N; Lambrechts, P; Bronckaers, A; Lambrichts, I Stem Cells Dev 2015-04-14 16.15 | Apr 20 Immune Checkpoint Targeting in Cancer Therapy: Toward Combination Strategies with Curative Potential Sharma, P; Allison, JP Cell 2015-04-09 16.14 | Apr 13 Adoptive Cell Transfer as Personalized Immunotherapy for Human Cancer Rosenberg, SA; Restifo. NP Science 2015-04-03 16.13 | Apr 6 The Future of Immune Checkpoint Therapy Sharma, P; Allison, JP Science 2015-04-03 16.13 | Apr 6 Advances and Challenges in Immunotherapy for Solid Organ and Hematopoietic Stem Cell Transplantation McDonald-Hyman, C; Turka, LA; Blazar, BR Sci Transl Med 2015-03-25 16.12 | Mar 30 Advances in CRISPR-Cas9 Genome Engineering: Lessons Learned from RNA Interference Barrangou, R; Birmingham, A; Wiemann, S; Beijersbergen, RL; Hornung, V; Smith, AV Nucleic Acids Res 2015-03-23 16.12 | Mar 30 Bladder Recovery by Stem Cell Based Cell Therapy in the Bladder Dysfunction Induced by Spinal Cord Injury: Systematic Review and Meta-Analysis Kim, JH; Shim, SR; Doo, SW; Yang, WJ; Yoo, BW; Kim, JM; Ko, YM; Song, ES; Lim, IS; Lee, HJ; Song, YS PLoS One 2015-03-17 16.11 | Mar 23 Adeno-Associated Virus-Mediated Gene Therapy in Cardiovascular Disease Hammoudi, N; Ishikawa, K; Hajjar, RJ Curr Opin Cardiol 2015-03-16 16.11 | Mar 23 Gene Therapy of Inherited Retinal Degenerations: Prospects and Challenges Trapani, I; Banfi, S; Simonelli, F; Surace, E; Auricchio, A Hum Gene Ther 2015-03-11 16.10 | Mar 16 Beyond Consolidation: Auto-SCT and Immunotherapy for Plasma Cell Myeloma Lendvai, N; Cohen, AD; Cho, HJ Bone Marrow Transplant 2015-03-09 16.10 | Mar 16 In Vivo Reprogramming for Tissue Repair Heinrich, C; Spagnoli, FM; Berninger, B Nat Cell Biol 2015-02-27 16.09 | Mar 9 Aptamer Nanomedicine for Cancer Therapeutics: Barriers and Potential for Translation Lao, YH; Phua, KK; Leong, KW ACS Nano 2015-03-03 16.09 | Mar 9 Manufacture of Tumor- and Virus-Specific T Lymphocytes for Adoptive Cell Therapies Wang, X; Riviere, I Cancer Gene Ther 2015-02-27 16.08 | Mar 2 Gene Therapy for Radioprotection Everett, WH; Curiel, DT Cancer Gene Ther 2015-02-27 16.08 | Mar 2 B-Cell Activating Factor in the Pathophysiology of Multiple Myeloma: A Target for Therapy? Hengeveld, PJ; Kersten, MJ Blood Cancer J 2015-02-27 16.08 | Mar 2 Humanized Models of Tumor Immunology in the 21st Century: Convergence of cancer Research and Tissue Engineering Holzapfel, BM; Wagner, F; Thibaudeau, L; Levesque, JP; Hutmacher, DW Stem Cells 2015-02-19 16.07 | Feb 23 Translational Data from Adeno-Associated Virus-Mediated Gene Therapy of Hemophilia B in Dogs Nichols, TC; Whitford, MH; Arruda, VR; Stedman, HH; Kay, MA; High, KA Hum Gene Ther Clin Dev 2015-02-12 16.06 | Feb 16 New Strategies in Glioblastoma: Exploiting the New Biology Fine, HA Clin Cancer Res 2015-02-10 16.06 | Feb 16 Stem Cells for Amyotrophic Lateral Sclerosis Modeling and Therapy: Myth or Fact? Coatti, GC; Beccari, MS; Olvio, TR; Mitne-Neto, M; Okamoto, OK; Zatz, M Cytometry A 2015-02-02 16.05 | Feb 9 The Potential Use of Cell-Based Therapies in the Treatment of Oral Diseases Kagami, H Oral Dis 2015-02-04 16.05 | Feb 9 Adoptive Immunotherapy with the Use of Regulatory T Cells and Virus-Specific T Cells Derived from Cord Blood Hanley, PJ; Bollard, CM; Brunstein, CG Cytotherapy 2015-01-24 16.04 | Jan 26 Gene and Cell Therapy for Pancreatic Cancer Singh, HM; Ungerechts, G; Tsimberidou, AM Expert Opin Biol Ther 2015-01-13 16.03 | Jan 26 Preclinical and Clinical Evidence for Stem Cell Therapies as Treatment for Diabetic Wounds Heublein, H; Bader, A; Giri, S Drug Discov Today 2015-01-17 16.03 | Jan 26 Respiratory Tissue Engineering: Current Status and Opportunities for the Future OLeary, C; Gilbert, JL; ODea, S; OBrien, FJ; Cryan, SA Tissue Eng Part B Rev 2015-01-14 16.02 | Jan 19 Tailoring Bioengineered Scaffolds for Stem Cell Applications in Tissue Engineering and Regenerative Medicine Cosson, S; Otte, EA; Hezaveh, H; Cooper-White, JJ Stem Cells Transl Med 2014-01-09 16.02 | Jan 19 Stromal Cells and Stem Cells in Clinical Bone Regeneration Grayson, WL; Bunnell, BA; Martin, E; Frazier, T; Hung, BP; Gimble, JM Nat Rev Endocrinol 2015-01-06 16.01 | Jan 12 Clinical Applications of Naturally Derived Biopolymer-Based Scaffolds for Regenerative Medicine Stoppel, WL; Ghezzi, CE; McNamara, SL; Iii, LD; Kaplan, DL Ann Biomed Eng 2014-12-24 16.00 | Jan 5 Valproic Acid-Mediated Neuroprotection and Neurogenesis after Spinal Cord Injury: From Mechanism to Clinical Potential Chu, T; Zhou, H; Lu, L; Kong, X; Wang, T; Pan, B; Feng, S Regen Med 2014-12-08 15.49 | Dec 15 Rate-Programming of Nano-Particulate Delivery Systems for Smart Bioactive Scaffolds in Tissue Engineering Izadifar, M1; Haddadi, A; Chen, X; Kelly, ME Nanotechnology 2014-12-04 15.48 | Dec 8 The New Frontier of Genome Engineering with CRISPR-Cas9 Doudna, JA; Charpentier, E Science 2014-11-28 15.47 | Dec 1 Aerosol Gene Delivery using Viral Vectors and Cationic Carriers for In Vivo Lung Cancer Therapy Hong, SH; Park, SJ; Lee, S; Cho, CS; Cho, MH Expert Opin Drug Deliv 2014-11-25 15.47 | Dec 1 Stem Cells and Muscle Diseases: Advances in Cell Therapy Strategies Negroni, E; Gidaro, T; Bigot, A; Butler-Browne, G; Mouly, V; Trollet, C Neuropathol Appl Neurobiol 2014-11-18 15.46 | Nov 24 Therapeutic Face of RNAi: In Vivo Challenges Borna, H; Imani, S; Iman, M; Azimzadeh Jamalkandi, S Expert Opin Biol Ther 2014-11-24 15.46 | Nov 24 Mesoangioblast and Mesenchymal Stem Cell Therapy for Muscular Dystrophy: Progress, Challenges, and Future Directions Berry, SE Stem Cells Transl Med 2014-11-12 15.45 | Nov 17 Chimeric Antigen Receptor T-Cell Therapy to Target Hematologic Malignancies Kenderian, SS; Ruella, M; Gill, S; Kalos, M Cancer Res 2014-11-04 15.44 | Nov 10 Prostate Cancer Immunotherapy: Beyond Immunity to Curability Simons, JW Cancer Immunol Res 2014-11-02 15.44 | Nov 10 EpsteinBarr Virus and Multiple Sclerosis: Potential Opportunities for Immunotherapy Pender, MP; Burrows, SR Clin Transl Immunol 2014-10-31 15.43 | Nov 3 Synthetic Lethality and Cancer Therapy: Lessons Learned from the Development of PARP Inhibitors Lord, CJ; Tutt, AN; Ashworth, A Annu Rev Med 2014-10-17 15.42 | Oct 27 Optimizing Drug Therapy in Pediatric SCT: Focus on Pharmacokinetics McCune, JS; Jacobson, P; Wiseman, A; Militano, O Bone Marrow Transplant 2014-10-27 15.42 | Oct 27 The potential Role for Regulatory T-Cell Therapy in Vascularized Composite Allograft Transplantation Issa, F; Wood, KJ Curr Opin Organ Transplant 2014-10-20 15.42 | Oct 27 Bone Marrow-Derived Stem Cell Therapy for Metastatic Brain Cancers Kaneko, Y; Tajiri, N; Staples, M; Reyes, S; Lozano, D; Sanberg, PR; Freeman, TB; van Loveren, H; Kim, SU; Borlongan, CV Cell Transplant 2014-10-10 15.41 | Oct 20 Gene Therapy for Inherited Muscle Diseases: Where Genetics Meets Rehabilitation Medicine Braun, R; Wang, Z; Mack, DL; Childers, MK Am J Phys Med Rehabil 2014-11-01 15.41 | Oct 20 Translational Research in Oncology10 Years of Progress and Future Prospects Doroshaw, JH; Kummar, S Nat Rev Clin Oncol 2014-10-07 15.40 | Oct 13 Stem Cell Transplantation for Primary Immunodeficiencies: The European Experience Cavazzana, M; Touzot, F; Moshous, D; Neven, B; Blanche, S; Fischer, A Curr Opin Allergy Clin Immunol 2014-10-10 15.40 | Oct 13 Gene Therapy for Autoimmune Disease Shu, SA; Wang, J; Tao, MH; Leung, PS Clin Rev Allergy Immunol 2014-10-03 15.39 | Oct 6 Mechanism-Based Cancer Therapy: Resistance to Therapy, Therapy for Resistance Ramos, P; Bentires-Alj, M Oncogene 2014-09-29 15.39 | Oct 6 Biomimetic Nanoparticles for siRNA Delivery in the Treatment of Leukemia Guoa, J; Cahillb, MR; McKennac, SL; ODriscoll, CM Biotech Adv 2014-09-16 15.38 | Sep 29 Biologic Scaffolds for Regenerative Medicine: Mechanisms of In Vivo Remodeling Londono, R; Badylak, SF Ann Biomed Eng 2014-09-12 15.37 | Sep 22 Progress in Gene Therapy for Primary Immunodeficiencies Using Lentiviral Vectors Sauer, AV; Di Lorenzo, B; Carriglio, N; Aiuti, A Curr Opin Allergy Clin Immunol 2014-09-08 15.36 | Sep 15 Tissue-Engineering-Based Strategies for Regenerative Endodontics Albuquerque, MT; Valera, MC; Nakashima, M; Nr, JE; Bottino, MC J Dent Res 2014-09-08 15.36 | Sep 15 New Generation Dendritic Cell Vaccine for Immunotherapy of Acute Myeloid Leukemia Subklewe, M; Geiger, C; Lichtenegger, FS; Javorovic, M; Kvalheim, G; Schendel, DJ; Bigalke, I Cancer Immunol Immunother 2014-09-04 15.36 | Sep 15 Similar Effect of Autologous and Allogeneic Cell Therapy for Ischemic Heart Disease: Systematic Review and Meta-Analysis of Large Animal Studies Jansen of Lorkeers, SJ; Eding, JE; Vesterinen, HM; van der Spoel, TI; Sena, ES; Duckers, HJ; Doevendans, PA; Macleod, MR; Chamuleau, SA Circ Res 2014-09-03 15.35 | Sep 8 Stem Cells: A Promising Source for Vascular Regenerative Medicine Rammal, H; Harmouch, C; Lataillade, JJ; Laurent-Maquin, D; Labrude, P; Menu, P; Kerdjoudj, H Stem Cells Dev 2014-08-28 15.34 | Sep 1 Gene Therapy for the Nervous System: Challenges and New Strategies Maguire, CA; Ramirez, SH; Merkel, SF; Sena-Esteves, M; Breakefield, XO Neurotherapeutics 2014-08-27 15.34 | Sep 1 Regenerative Medicine for the Heart: Perspectives on Stem-Cell Therapy Cho, GS; Fernandez, L; Kwon, C Antioxid Redox Signal 2014-08-18 15.33 | Aug 25 Recent Advances of Stem Cell Therapy for Retinitis Pigmentosa He, Y;, Zhang, Y; Liu, X; Ghazaryan, E; Li, Y; Xie, J; Su, G Prog Retin Eye Res 2014-08-20 15.33 | Aug 25 Vector Platforms for Gene Therapy of Inherited Retinopathies Trapani, I; Puppo, A; Auricchio, A Prog Retin Eye Res 2014-08-11 15.32 | Aug 18 Airway Tissue Engineering: An Update Fishman, JM;, Wiles, K; Lowdell, MW; De Coppi, P; Elliott, MJ; Atala, A; Birchall, MA Expert Opin Biol Ther 2014-08-07 15.31 | Aug 11 A Systematic Review of Preclinical Studies on the Therapeutic Potential of Mesenchymal Stromal Cell-Derived Microvesicles Akyurekli, C; Le, Y; Richardson, RB; Fergusson, D; Tay, J; Allan, DS Stem Cell Rev 2014-08-05 15.31 | Aug 11 Genomic Instability in Human Stem Cells: Current Status and Future Challenges Oliveira, PH; Silva, CL; Cabral, JMS Stem Cells 2014-07-30 15.30 | Aug 4 Caveats of Mesenchymal Stem Cell Therapy in Solid Organ Transplantation Haarer, J; Johnson, CL; Soeder, Y; Dahlke, MH Transpl Int 2014-07-31 15.30 | Aug 4 Improved Mouse Models to Assess Tumor Immunity and irAEs after Combination Cancer Immunotherapies Liu, J; 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Exploiting Novel Gene and Cell Therapy Strategies for Muscular Dystrophies Benedetti, S; Hoshiya, H; Tedesco, FS FEBS J 2013-03-04 14.05 | Feb 11 Gene Therapy for Malignant Mesothelioma: Current Prospects and Challenges Tagawa, M; Tada, Y; Shimada, H; Hiroshima, K Cancer Gene Ther 2013-02-08 14.05 | Feb 11 Steps Toward Safe Cell Therapy Using Induced Pluripotent Stem Cells Okano, H; Nakamura, M; Yoshida, K; Okada, Y; Tsuji, O; Nori, S; Ikeda, E; Yamanaka, S; Miura, K Circ Res 2013-02-01 14.04 | Feb 4 In Vivo Reprogramming in Inflammatory Bowel Disease Wagnerova, A; Gardlik, R Gene Ther 2013-09-12 14.36 | Sep 16 Reprogrammed Cells for Disease Modeling and Regenerative Medicine Cherry, A; Daley, G Annu Rev Med 2012-01-01 14.03 | Jan 28 Cell and Gene Therapy in Alzheimers Disease Glat, MJ; Offen, D Stem Cells Dev 2013-01-16 14.03 | Jan 28 Gene Therapy for Hemoglobinopathies: Progress and Challenge Dong, A; Rivella, S; Breda, L Transl Res 2013-01-21 14.03 | Jan 28 Adult Salivary Gland Stem Cells and a Potential Therapy for Xerostomia Pringle, S; Van Os, R; Coppes, RP Stem Cells 2013-03-24 14.02 | Jan 21 Mesenchymal Stem Cells and the Lung Sinclair, K; Yerkovich, ST; Chambers, DC Respirology 2013-03-21 14.02 | Jan 21 IL-27 in Tumor Immunity and Immunotherapy Murugaiyan, G; Saha, B Trends Mol Med 2013-01-08 14.01 | Jan 14 Recent Developments in Oncolytic Adenovirus-Based Immunotherapeutic Agents for Use against Metastatic Cancers Choi, IK; Yun, CO Cancer Gene Ther 2013-01-11 14.01 | Jan 14 Human Mesenchymal Stem Cells and Their Paracrine Factors for the Treatment of Brain Tumors Chan, JKY; Lam, PYP Hum Gene Ther 2013-09-20 14.37 | Sep 23 Chemical Approaches to Stem Cell Biology and Therapeutics Li, W; Li, K; Wei, W; Ding, S Cell Stem Cell 2013-09-05 14.35 | Sep 9 The Role of Mesenchymal Stromal Cells in Spinal Cord Injury, Regenerative Medicine and Possible Clinical Applications Forostyak, S; Jendelova, P; Sykova, E Biochimie 2013-08-27 14.35 | Sep 9 Priming Adult Stem Cells by Hypoxic Pretreatments for Applications in Regenerative Medicine Muscari, C; Giordano, E; Bonaf, F; Govoni, M; Pasini, A; Guarnieri, C J Biomed Sci 2013-08-29 14.34 | Sep 2 Cell Therapy for Heart Failure: A Comprehensive Overview of Experimental and Clinical Studies, Current Challenges, and Future Directions Sanganalmath, SK; Bolli, R Circ Res 2013-07-25 14.34 | Sep 2 Tumorigenicity as a Clinical Hurdle for Pluripotent Stem Cell Therapies Lee, AS; Tang, C; Rao, MS; Weissman, IL; We, JC Nat Med 2013-08-06 14.33 | Aug 26 Technological Progress and Challenges towards cGMP Manufacturing of Human Pluripotent Stem Cells Based Therapeutic Products for Allogeneic and Autologous Cell Therapies Abbasalizadeh, S; Baharvand, H Biotechnol Adv 2013-08-17 14.33 | Aug 26 Back to the Future: How Human Induced Pluripotent Stem Cells will Transform Regenerative Medicine Svendsen, CN Hum Mol Genet 2013-08-14 14.32 | Aug 19 Cancer Gene Discovery: Exploiting Insertional Mutagenesis Ranzani, M; Annunziato, S; Adams, DJ; Montini, E Mol Can Res 2013-08-08 14.31 | Aug 12 CD34+ Stem Cell Therapy in Non-Ischemic Dilated Cardiomyopathy Patients Vrtovec, B; Poglajen, G; Sever, M; Lezaic, L; Socan, A; Haddad, F; Wu, JC Clin Pharmacol Ther 2013-07-31 14.30 | Aug 5 Cell Therapy for Cystic Fibrosis Murphy, SV; Atala, A J Tissue Eng Regen Med 2013-07-25 14.30 | Aug 5 Cord Blood Transplantation for Cure of HIV Infections Petz, L Stem Cells Transl Med 2013-07-24 14.29 | Jul 29 Mesenchymal Stem Cells in Joint Disease and Repair Barry, F; Murphy, M Nat Rev Rheumatol 2013-07-23 14.29 | Jul 29 Vascular Endothelial Growth Factor in Heart Failure Taimeh, Z; Loughran, J; Birks, EJ; Bolli, R Nat Rev Cardiol 2013-07-16 14.28 | Jul 22 Clinical Programs of Stem Cell Therapies for Liver and Pancreas Lanzoni, G; Oikawa, T; Wang, Y; Cui, CB; Carpino, G; Cardinale, V; Gerber, D; Gabriel, M; Dominguez-Bendala, J; Furth, ME; Gaudio, E; Alvaro, D; Inverardi, L; Reid, LM Stem Cells 2013-08-19 14.28 | Jul 22 Safety of Intra-Articular Cell-Therapy with Culture-Expanded Stem Cells in Humans: A Systematic Literature Review Peeters, CMM; Leijs, MJC; Reijman, M; van Osch, GJVM; Bos, PK Osteoarthritis Cartilage 2013-10-01 14.27 | Jul 15 Cell Therapy, a Novel Remedy for Dilated Cardiomyopathy? A Systematic Review Gho, J; Kummeling, G; Koudstaal, S; Jansen of Lorkeers, S; Doevendans, P; Asselbergs, F; Chamuleau, S J Card Fail 2013-05-13 14.27 | Jul 15 Induced Regeneration The Progress and Promise of Direct Reprogramming for Heart Repair Addis, RC; Epstein, JA Nat Med 2013-07-08 14.26 | Jul 8 Immunotherapy with Gene-Modified T Cells: Limiting Side Effects Provides New Challenges Stauss, HJ; Morris, EC Gene Ther 2013-06-27 14.26 | Jul 8 Engineering In Vitro Microenvironments for Cell Based Therapies and Drug Discovery Cigognini, D; Lomas, A; Kumar, P; Satyam, A; English, A; Azeem, A; Pandit, A; Zeugolis, D Drug Discov Today 2013-06-25 14.25 | Jul 1 The Functions and Applications of RGD in Tumor Therapy and Tissue Engineering Wang, F; Li, Y; Shen, Y; Wang, A; Wang, S; Xie, T Int J Mol Sci 2013-06-27 14.25 | Jul 1 Adult Mesenchymal Stromal Cell Therapy for Inflammatory Diseases: How Well Are We Joining the Dots? Griffin, M; Elliman, S; Cahill, E; English, K; Ceredig, R; Ritter, T Stem Cells 2013-06-14 14.24 | Jun 24 Mesenchymal Stem Cell Treatment for Ischemic Kidney Disease Zhu, XY; Lerman, A; Lerman, L Stem Cells 2013-06-14 14.23 | Jun 17 Evidence for High Translational Potential of Mesenchymal Stromal Cell Therapy to Improve Recovery from Ischemic Stroke Eckert, M; Vu, Q; Xie, K; Yu, J; Liao, W; Cramer, S; Zhao, W J Cereb Blood Flow Metab 2013-06-12 14.23 | Jun 17 The Role of Gene Therapy in Regenerative Surgery: Updated Insights Giatsidis, G; Venezia, ED; Basseto, F Plast Reconstr Surg 2013-06-01 14.21 | Jun 3 Mesenchymal Stem Cells as Vectors for Lung Cancer Therapy Kolluri, KK; Laurent, GB; Janes, SM Respiration 2013-05-23 14.21 | Jun 3 Immunotherapy: Adoptive Cell Therapy Simplified Kirk, R Nat Rev Clin Oncol 2013-05-21 14.20 | May 27 Therapeutic Angiogenesis for Critical Limb Ischemia Annex, BH Nat Rev Cardiol 2013-05-14 14.19 | May 20 Cell-Based Immunotherapy against Gliomas: From Bench to Bedside Bovenberg, MSS; Degeling, MH; Tannous, BA Mol Ther 2013-05-07 14.18 | May 13 Cellular Immunotherapy for Plasma Cell Myeloma Garfall, AL; Vogl, DT; Weiss, BM; Stadtmauer, EA Bone Marrow Transplant 2013-05-06 14.18 | May 13 Regulation of Stem Cell Therapies Under Attack in Europe: For Whom the Bell Tolls Bianco, P; Barker, R; Brstle, O; Cattaneo, E; Clevers, H; Daley, GQ; De Luca, M; Goldstein, L; Lindvall, O; Mummery, C; Robey, PG; Sattler de Sousa e Brito, C; Smith, A EMBO J 2013-05-03 14.17 | May 6 Progress in Gene Therapy for Neurological Disorders Simonato, M; Bennett, J; Boulis, NM; Castro, MG; Fink, DJ; Goins, WF; Gray, SJ; Lowenstein, PR; Vandenberghe, LH; Wilson, TJ; Wolfe, JH; Glorioso, JC Nat Rev Neurol 2013-04-23 14.16 | Apr 29 Cell Therapy of Peripheral Arterial Disease: From Experimental Findings to Clinical Trials Raval, Z; Losordo, DW Circ Res 2013-04-26 14.16 | Apr 29 Immune Responses to AAV Vectors: Overcoming Barriers to Successful Gene Therapy Mingozzi, F; High, KA Blood 2013-04-17 14.15 | Apr 22 Smelling the Roses and Seeing the Light: Gene Therapy for Ciliopathies McIntyre, JC; Williams, CL; Martens, JR Trends Biotechnol 2013-04-17 14.15 | Apr 22 Molecular Imaging: The Key to Advancing Cardiac Stem Cell Therapy Chen, IY; Wu; JC Trends Cardiovasc Med 2013-04-03 14.14 | Apr 15 Therapeutic Angiogenesis for Revascularization in Peripheral Artery Disease Grochot-Przeczek, A; Dulak, J; Jozkowicz, A Gene 2013-04-05 14.14 | Apr 15 Cell-Based Therapeutics: The Next Pillar of Medicine Fischbach, MA; Bluestone, JA; Lim, WA Sci Transl Med 2013-04-03 14.13 | Apr 8 Advances in Stem Cell Therapy against Gliomas Bovenberg, MSS; Degeling, MH; Tannous, BA Trends Mol Med 2013-03-25 14.12 | Apr 1 The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies Rosado-de-Castro, PH; Pimentel-Coelho, PM; Barbosa da Fonseca, LM; Rodriguez de Freitas, G; Mendez-Otero, R Stem Cells Dev 2013-04-25 14.11 | Mar 25 Interaction between Natural Killer Cells and Regulatory T Cells: Perspectives for Immunotherapy Pedroza-Pacheco, I; Madrigal, A; Saudemont, A Cell Mol Immunol 2013-03-25 14.11 | Mar 25 Delivering RNAi Therapeutics with Non-Viral Technology: A Promising Strategy for Prostate Cancer? Guo, J; Evans, JC; ODriscoll, CM Trends Mol Med 2013-03-14 14.10 | Mar 18 Cortical Interneurons from Human Pluripotent Stem Cells: Prospects for Neurological and Psychiatric Disease Arber, C; Li, M Front Cell Neurosci 2013-03-13 14.10 | Mar 18 From Bench to Bedside: Review of Gene and Cell-Based Therapies and the Slow Advancement into Phase III Clinical Trials, with a Focus on Aastroms Ixmyelocel-T Bartel, RL; Booth, E; Cramer, C; Ledford, K; Watling, S; Zeigler, F Stem Cell Rev 2013-03-01 14.09 | Mar11 The Innovative Evolution of Cancer Gene and Cellular Therapies Lam, P; Khan, G; Stripecke, R; Hui, KM; Kasahara, N; Peng, KW; Guinn, BA Cancer Gene Ther 2013-02-01 14.04 | Feb 4

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Treatment | Stemgenn

Thursday, August 4th, 2016

A single cell that can replicate itself and differentiate into many cell types. Therefore it is called the master cell of our body. When a stem cell divides, each new cell has the potential to remain a stem cell or become another type of cell with a more specialized function i.e. muscle cell, red blood cell, liver cell, brain cell, etc.Stem cells exhibit inherent properties of plasticity, homing, engraftment and self renewal. This capacity to regenerate into various cell types holdshuge clinical potentials.

Stem Cell is the master cell of our and can give rise to any kind of cells. Ideally stem cells are classified as embryonic, adult, foetal and induced pluripotent stem cells. Stem Cells are pluripotent, totipotent and multipoint.

Regenerative cell functions include:

Mainly stem cells are of two types: embryonic and adult. We use adult stem cells for treatment which are found inbone marrow, adipose tissue, peripheral blood, dental pulp, cord blood, menstrual blood etc.

Cells removed from a patient and replaced during the same surgical procedure pose no greater risk of disease transmission than the surgery itself. FDA Regulation of Stem Cell Based Therapies, Halme and Kessler, New England Journal of Medicine, 2006.

The fat from the mini- liposuction is processed using a combination of centrifuge and incubation.Cellular compositions of the SVF areadult mesenchymal stem cells, pre-adipocytes, endothelial cells (thin layer of cells that lines the interior surface of blood vessels), smooth muscle cells, connective tissue, fibroblasts, growth factors.

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Cell therapy could slow decline in heart failure patients …

Thursday, August 4th, 2016

But that means about 2.5 million Americans live with heart failure that blocks blood vessels and reduces blood supply to the body.

A new study provides an early indication that cell therapy using cells from bone marrow could one day help treat heart failure.

Researchers gave 60 patients with heart failure an injection of the therapy in the heart and compared their rates of death and heart problems to those of 66 similar patients who received a placebo injection of saltwater in the heart.

The researchers found that, during the year following the treatment, the patients who received the cell therapy had a 37% lower rate of death and hospitalization for heart failure-related problems, such as fluid buildup in the body or shortness of breath, compared with the placebo group. In the cell therapy group, 3.4% of the patients died and 51.7% were hospitalized for heart problems, whereas 13.7% of the placebo group died and 82.4% were hospitalized.

In the year after the injection, 20.3% of the patients in the cell therapy group experienced an adverse event such as infection or stroke, compared with 41.8% of the placebo group. "It was surprising that the (placebo) patients did significantly worse," Patel said. This could have been because they underwent the same invasive procedures as the treatment group, but did not receive the same potentially beneficial cell therapy, which could have anti-inflammatory effects that decreased adverse events, he said.

Nevertheless, this therapy will need to be tested on more patients, Povsic said. "Although the study in The Lancet is very encouraging, it's still a relatively small study by cardiovascular standards. In heart disease we typically study hundreds to thousands of patients," he said.

The researchers and Vericel are hoping to start a larger phase 3 clinical trial of Ixmyelocel-T that includes more heart failure patients. The new study was a phase 2 trial, and these trials generally focus on establishing the effectiveness and safety of a new therapy.

Earlier cell therapies used all the cells in the bone marrow instead of selecting for certain types of cells, and thus might have been diluting their beneficial effects, Povsic said. "We are moving more and more away from first generation cell therapy," said Povsic, who is involved in two ongoing trials looking at the effect of selected cells from bone marrow in patients with heart failure or angina, a type of heart disease that reduces blood supply to the heart.

No cell therapies have been approved worldwide for heart failure patients. There are also no approved cell therapies for other types of heart disease in the United States, but several therapies are available in Asia, including a stem cell-based treatment for people who have had a heart attack.

The therapy in the new study would be appropriate for patients who have heart failure and are getting worse, despite taking medicines such as beta blockers and ACE inhibitors, Patel said. Nearly all the patients in the study were on one of these drugs. However, the therapy would not be appropriate for patients whose heart failure is so bad that they are often hospitalized for heart complications, Patel said. These patients would be candidates for a heart transplant or left ventricular assist device.

"There's a growing population of (heart failure) patients that are on medicines and who continue to have significant symptoms," Povsic said.

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Issues Archive – Cell Therapy News

Thursday, August 4th, 2016

Biogen Announces Collaboration with University of Pennsylvania on Multiple Gene Therapy Programs

Biogen announced a broad collaboration and alliance with the University of Pennsylvania to advance gene therapy and gene editing technologies. The expansive research and translational development collaboration has multiple objectives, but will primarily focus on the development of therapeutic approaches that target the eye, skeletal muscle and the central nervous system. [Biogen] PressRelease

State Stem Cell Agency Awards Stanford Researchers

Albert Wong receives $2.9 million to develop vaccine for glioblastoma; four others awarded $240,000 each to study bladder, heart and eye conditions. [Stanford School of Medicine] PressRelease

MJFF Supports Stem Cell Projects to Explore Therapies and Provide Research Tools

The Michael J. Fox Foundation (MJFF) announced funding for two projects leveraging the promise of engineered stem cells to speed new therapies and deeper understanding of Parkinsons disease. [The Michael J. Fox Foundation] PressRelease

Novel Immunotherapy Trial for Lymphoma Offers Hope to Patients at Sylvester

Researchers are testing a novel cellular immunotherapy approach to treating patients with diffuse large B-cell lymphoma who have failed standard therapy. This investigational anti-CD19 chimeric antigen receptor T cell therapy, known as KTE-C19, is being studied in a Phase II clinical trial for patients with aggressive non-Hodgkins lymphoma. [University of Miami Miller School of Medicine] PressRelease

Asterias Biotherapeutics Announces Positive New Long-Term Follow-Up Results for AST-OPC1

Asterias Biotherapeutics, Inc. announced new positive long-term follow-up results from its Phase I clinical trial assessing the safety of AST-OPC1 (oligodendrocyte progenitor cells) in patients with spinal cord injury. [Asterias Biotherapeutics, Inc.] PressRelease

FDA Grants Roches Cancer Immunotherapy Tecentriq (Atezolizumab) Accelerated Approval for People with a Specific Type of Advanced Bladder Cancereneration CAR Modifications for Enhanced T-Cell Function

Roche announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Tecentriq for the treatment of people with locally advanced or metastatic urothelial carcinoma. [F. Hoffmann-La Roche Ltd.] PressRelease

Nano Dimension and Accellta Joined Forces to Successfully BioPrint Stem Cell-Derived Tissues

Nano Dimension Ltd. announced it has successfully lab-tested a proof of concept 3D Bioprinter for stem cells. The trial was conducted in collaboration with Accellta Ltd. [Nano Dimension Ltd. (PR Newswire Association LLC.)] PressRelease

Regen BioPharma, Inc. Announces ucVax: Universal Donor Cancer Cellular Immunotherapy

Regen BioPharma, Inc. and announced initiation of a preclinical development program aimed at creating the first cord blood based cancer immunotherapeutic product leveraging its NR2F6 immunological checkpoint. [Regen BioPharma, Inc. (PR Newswire Association LLC.)] PressRelease

VM BioPharma Announces FDA Fast Track Designation Granted for Investigational Gene Therapy VM202 for Patients with Amyotrophic Lateral Sclerosis (ALS)

VM BioPharma announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the companys lead investigational drug, VM202, a Phase II novel gene therapy for the potential treatment of Amyotrophic Lateral Sclerosis. [VM BioPharma] PressRelease

Cryoport to Provide Cold Chain Logistics Support for International Stem Cell Corporations Phase I Clinical Trial for the Treatment of Parkinsons Disease

Cryoport, Inc. announced that it will provide global logistics support to International Stem Cell Corporations (ISCO) Phase I clinical trial in Australia for the treatment of moderate to severe Parkinsons disease. ISCO commenced patient enrollment for the study earlier this month. [Cryoport, Inc.] PressRelease

WPI Team Awarded Patent for Reprograming Skin Cells

Cell therapies for a range of serious conditions, including heart attacks, diabetes, and traumatic injuries, will be accelerated by research at Worcester Polytechnic Institute (WPI) that yielded a newly patented method of converting human skin cells into engines of wound healing and tissue regeneration. [Worcester Polytechnic Institute] PressRelease

Caladrius Biosciences Licenses Cell Therapy Technology for Ovarian Cancer and Subleases Irvine Facility to AiVita Biomedical

Caladrius Biosciences, Inc. announces that it has licensed to AiVita Biomedical, Inc. the exclusive global rights to its tumor cell/dendritic cell technology for the treatment of ovarian cancer. [Caladrius Biosciences] PressRelease

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Worlds leading Stem Cell Conference | Global Meetings …

Thursday, August 4th, 2016

Conference Series LLCinvites all the participants from all over the world to attend '8th World Congress on Cell & Stem Cell Research during March 20-22, 2017 in Orlando, USA which includes prompt keynote presentations, Oral talks, Poster presentations and Exhibitions.

Stem cellsare cells originate in all multi-cellular organisms. They were isolated in mice in 1981 and in humans in 1998. In humans there are several types of stem cells, each with variable levels of potency. Stem cell treatments are a type of cell therapy that introduces new cells into adult bodies for possible treatment of cancer, diabetes, neurological disorders and other medical conditions. Stem cells have been used to repair tissue damaged by disease or age.

Objective

Stem Cell Research-2017 has the platform to fulfill the prevailing gaps in the transformation of this science of hope, to serve promptly with solutions to all in the need. Stem Cell Research 2017 will have an anticipated participation of 120+ delegates across the world to discuss the conference goal.

Success Story: Cell Science Conference Series

The success of the Cell Science conference series has given us the prospect to bring the gathering inOrlando,USA. Since its commencement in 2011 Cell Science series has witnessed around 750 researchers of great potentials and outstanding research presentations from around the world. Awareness of stem cells and its application is becoming popular among the general population. Parallel offers of hope add woes to the researchers of cell science due to the potential limitations experienced in the real-time.

About Organizers

Conference Series LLCis one of the leadingOpen Access publishersand organizers of international scientificconferences and events every year across USA, Europe & Asia Conference Series LLChas so far organized 3000+Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on Medical, Pharma, Engineering, Science, Technology and Business with 700+ peer-reviewed open accessjournalsin basic science, health, and technology. OMICS International is also in association with more than 1000 International scientific and technological societies and associations and a team of 30,000 eminent scholars, reputed scientists as editorial board members.

Scientific Sessions

Stem Cell Research-2017 will encompass recent researches and findings in stem cell technologies, stem cell therapies and transplantations, current understanding of cell plasticity in cancer and other advancements in stem cell research and cell science.Stem Cell Research-2017 will be a great platform for research scientists and young researchers to share their current findings in this field of applied science. The major scientific sessions in Stem Cell Research-2017will focus on the latest and exciting innovations in prominent areas of cell science and stem cell research.

Target Audience:

Eminent personalities, Directors, CEO, President, Vice-president, Organizations, Associations heads and Professors, Research scientists, Stem Cell laboratory heads, Post-docs, Students other affiliates related to the area of Stem cell research, stem cell line companies can be as Target Audience.

8th World Congress on Cell & Stem Cell Research

The success of the 7 Cell Science conferences series has given us the prospect to bring the gathering one more time for our 8thWorld Congress 2017 meet in Orlando, USA. Since its commencement in 2011 cell science series has perceived around 750 researchers of great potentials and outstanding research presentations around the globe. The awareness of stem cells and its application is increasing among the general population that also in parallel offers hope and add woes to the researchers of cell science due to the potential limitations experienced in the real-time.

Stem Cell Research-2017has the goal to fill the prevailing gaps in the transformation of this science of hope to promptly serve solutions to all in the need.World Congress 2017 will have an anticipated participation of 100-120 delegates from around the world to discuss the conference goal.

History of Stem cells Research

Stem cells have an interesting history, in the mid-1800s it was revealed that cells were basically the building blocks of life and that some cells had the ability to produce other cells. Efforts were made to fertilize mammalian eggs outside of the human body and in the early 1900s, it was discovered that some cells had the capacity to generate blood cells. In 1968, the first bone marrow transplant was achieved successfully to treat two siblings with severe combined immunodeficiency. Other significant events in stem cell research include:

1978: Stem cells were discovered in human cord blood 1981: First in vitro stem cell line developed from mice 1988: Embryonic stem cell lines created from a hamster 1995: First embryonic stem cell line derived from a primate 1997: Cloned lamb from stem cells 1997: Leukaemia origin found as haematopoietic stem cell, indicating possible proof of cancer stem cells

Funding in USA:

No federal law forever did embargo stem cell research in the United States, but only placed restrictions on funding and use, under Congress's power to spend. By executive order on March 9, 2009, President Barack Obama removed certain restrictions on federal funding for research involving new lines of humanembryonic stem cells. Prior to President Obama's executive order, federal funding was limited to non-embryonic stem cell research and embryonic stem cell research based uponembryonic stem celllines in existence prior to August 9, 2001. In 2011, a United States District Court "threw out a lawsuit that challenged the use of federal funds for embryonic stem cell research.

Members Associated with Stem Cell Research:

Discussion on Development, Regeneration, and Stem Cell Biology takes an interdisciplinary approach to understanding the fundamental question of how a single cell, the fertilized egg, ultimately produces a complex fully patterned adult organism, as well as the intimately related question of how adult structures regenerate. Stem cells play critical roles both during embryonic development and in later renewal and repair. More than 65 faculties in Philadelphia from both basic science and clinical departments in the Division of Biological Sciences belong to Development, Regeneration, and Stem Cell Biology. Their research uses traditional model species including nematode worms, fruit-flies, Arabidopsis, zebrafish, amphibians, chick and mouse as well as non-traditional model systems such as lampreys and cephalopods. Areas of research focus include stem cell biology, regeneration, developmental genetics, and cellular basis of development, developmental neurobiology, and evo-devo (Evolutionary developmental biology).

Stem Cell Market Value:

Worldwide many companies are developing and marketing specialized cell culture media, cell separation products, instruments and other reagents for life sciences research. We are providing a unique platform for the discussions between academia and business.

Global Tissue Engineering & Cell Therapy Market, By Region, 2009 2018

$Million

Why to attend???

Stem Cell Research-2017 could be an outstanding event that brings along a novel and International mixture of researchers, doctors, leading universities and stem cell analysis establishments creating the conference an ideal platform to share knowledge, adoptive collaborations across trade and world, and assess rising technologies across the world. World-renowned speakers, the most recent techniques, tactics, and the newest updates in cell science fields are assurances of this conference.

A Unique Opportunity for Advertisers and Sponsors at this International event:

http://stemcell.omicsgroup.com/sponsors.php

UAS Major Universities which deals with Stem Cell Research

University of Washington/Hutchinson Cancer Center

Oregon Stem Cell Center

University of California Davis

University of California San Francisco

University of California Berkeley

Stanford University

Mayo Clinic

Major Stem Cell Organization Worldwide:

Norwegian Center for Stem Cell Research

France I-stem

Stem Cell & Regenerative Medicine Ctr, Beijing

Stem Cell Research Centre, Korea

NSW Stem Cell Network

Monash University of Stem Cell Labs

Australian Stem Cell Centre

Target Audience:

Eminent personalities, Directors, CEO, President, Vice-president, Organizations, Associations heads and Professors, Research scientists, Stem Cell laboratory heads, Post-docs, Students other affiliates related to the area of Stem cell research, stem cell line companies can be as Target Audience

Market Analysis of Stem Cell Therapy:

The global market for stem cell products was $3.8 billion in 2011. This market is expected to reach nearly $4.3 billion in 2012 and $6.6 billion by 2016, increasing at a compound annual growth rate (CAGR) of 11.7% from 2011 to 2016.

Americas is the largest region of global stem cell market, with a market share of about $2.0 billion in 2013. The region is projected to increase to nearly $3.9 billion by 2018, with a CAGR of 13.9% for the period of 2013 to 2018

Europe is the second largest segment of the global stem cell market and is expected to grow at a CAGR of 13.4% reaching about $2.4 billion by 2018 from nearly $1.4 billion in 2013.

Figure 2:Global Market

Companies working for Stem Cells:

Company

Location

Business Type

Cynata Therapeutics

Armadale, Australia

Stem Cell Manufacturing Technology

Mesoblast

Melbourne, Australia

Regenerative Medicine

Activartis

Vienna, Austria

Dendritic Cell-Based Cancer Immunotherapy

Aposcience

Vienna, Austria

Treatments composed of mixture of cytokines, growth factors and other active components

Cardio3 Biosciences

Mont-Saint-Guibert, Belgium

Stem Cell Differentiation

Orthocyte (BioTime)

Alameda, CA

Cellular Therapies

Capricor

Beverly Hills, CA

Stem Cell Heart Treatments

Life Stem Genetics

Beverly Hills, CA

Autologous stem cell therapy

International Stem Cell

Carlsbad, CA

Proprietary Stem Cell Induction

Targazyme

Carlsbad, CA

Cell Therapy

DaVinci Biosciences

Costa Mesa, CA

Cellular Therapies

Invitrx Therapeutics

Irvine, CA

Autologous Stem Cell Therapy, Therapeutic & Cosmetic

Stem Cell Softwares :

Products Manufactured By Industry Related to Stem Cell:

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Eli and Edythe Broad Center of Regeneration Medicine and …

Wednesday, October 28th, 2015

Welcome to the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, one of the largest and most comprehensive programs of its kind in the United States.

In some 125 labs, scientists are carrying out studies, in cell culture and animals, aimed at understanding and developing treatment strategies for such conditions as heart disease, diabetes, epilepsy, multiple sclerosis, Parkinsons disease, Lou Gehrigs disease, spinal cord injury and cancer.

While the scientific foundation for the field is still being laid, UCSF scientists are beginning to move their work toward human clinical trials. A team of pediatric specialists and neurosurgeons is carrying out the second brain stem cell clinical trial ever conducted in the United States, focusing on a rare disease, inherited in boys, known as Pelizaeus-Merzbacher disease.

Others are working to develop strategies for treating diabetes, brain tumors, liver disease and epilepsy. The approach for treating epilepsy potentially also could be used to treat Parkinsons disease, as well as the pain and spasticity that follow brain and spinal cord injury.

The center is structured along seven research pipelines aimed at driving discoveries from the lab bench to the patient. Each pipeline focuses on a different organ system, including the blood, pancreas, liver, heart, reproductive organs, nervous system, musculoskeletal tissues and skin. And each of these pipelines is overseen by two leaders of international standing one representing the basic sciences and one representing clinical research. This approach has proven successful in the private sector for driving the development of new therapies.

The center, like all of UCSF, fosters a highly collaborative culture, encouraging a cross-pollination of ideas among scientists of different disciplines and years of experience. Researchers studying pancreatic beta cells damaged in diabetes collaborate with those who study nervous system diseases because stem cells undergo similar molecular signaling on the way to becoming both cell types. The opportunity to work in this culture has drawn some of the countrys premier young scientists to the center.

While the focus of the science is the future, UCSFs history in the field dates back to 1981, when Gail Martin, PhD, co-discovered embryonic stem cells in mice and coined the term embryonic stem cell. Two decades later, UCSFs Roger Pedersen, PhD, developed two of the first human embryonic stem cell lines, following the groundbreaking discovery by University of Wisconsins James Thomson, PhD, of a way to derive the cells.

Today, the Universitys faculty includes Shinya Yamanaka, MD, PhD, of the UCSF-affiliated J. David Gladstone Institutes and Kyoto University. His discovery in 2006 of a way to reprogram ordinary skin cells back to an embryonic-like state has given hope that someday these cells might be used in regenerative medicine.

Yamanakas seminal finding highlights the unexpected and dramatic discoveries that can characterize scientific research. In labs throughout UCSF and beyond, the goal is to move such findings into patients.

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CAR T-Cell Immunotherapy for ALL – National Cancer Institute

Tuesday, October 27th, 2015

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For years, the cornerstones of cancer treatment have been surgery, chemotherapy, and radiation therapy. Over the last decade, targeted therapies like imatinib (Gleevec) and trastuzumab (Herceptin)drugs that target cancer cells by homing in on specific molecular changes seen primarily in those cellshave also emerged as standard treatments for a number of cancers.

Illustration of the components of second- and third-generation chimeric antigen receptor T cells. (Adapted by permission from the American Association for Cancer Research: Lee, DW et al. The Future Is Now: Chimeric Antigen Receptors as New Targeted Therapies for Childhood Cancer. Clin Cancer Res; 2012;18(10); 278090. doi:10.1158/1078-0432.CCR-11-1920)

And now, despite years of starts and stutter steps, excitement is growing for immunotherapytherapies that harness the power of a patients immune system to combat their disease, or what some in the research community are calling the fifth pillar of cancer treatment.

One approach to immunotherapy involves engineering patients own immune cells to recognize and attack their tumors. And although this approach, called adoptive cell transfer (ACT), has been restricted to small clinical trials so far, treatments using these engineered immune cells have generated some remarkable responses in patients with advanced cancer.

For example, in several early-stage trials testing ACT in patients with advanced acute lymphoblastic leukemia (ALL) who had few if any remaining treatment options, many patients cancers have disappeared entirely. Several of these patients have remained cancer free for extended periods.

Equally promising results have been reported in several small trials involving patients with lymphoma.

These are small clinical trials, their lead investigators cautioned, and much more research is needed.

But the results from the trials performed thus far are proof of principle that we can successfully alter patients T cells so that they attack their cancer cells, said one of the trial's leaders, Renier J. Brentjens, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center (MSKCC) in New York.

Adoptive cell transfer is like giving patients a living drug, continued Dr. Brentjens.

Thats because ACTs building blocks are T cells, a type of immune cell collected from the patients own blood. After collection, the T cells are genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs). CARs are proteins that allow the T cells to recognize a specific protein (antigen) on tumor cells. These engineered CAR T cells are then grown in the laboratory until they number in the billions.

The expanded population of CAR T cells is then infused into the patient. After the infusion, if all goes as planned, the T cells multiply in the patients body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbor the antigen on their surfaces.

Although adoptive cell transfer has been restricted to small clinical trials so far, treatments using these engineered immune cells have generated some remarkable responses in patients with advanced cancer.

This process builds on a similar form of ACT pioneered by Steven Rosenberg, M.D., Ph.D., and his colleagues from NCIs Surgery Branch for patients with advanced melanoma.

The CAR T cells are much more potent than anything we can achieve with other immune-based treatments being studied, said Crystal Mackall, M.D., of NCIs Pediatric Oncology Branch (POB).

Even so, investigators working in this field caution that there is still much to learn about CAR T-cell therapy. But the early results from trials like these have generated considerable optimism.

CAR T-cell therapy eventually may become a standard therapy for some B-cell malignancies like ALL and chronic lymphocytic leukemia, Dr. Rosenberg wrote in a Nature Reviews Clinical Oncology article.

More than 80 percent of children who are diagnosed with ALL that arises in B cellsthe predominant type of pediatric ALLwill be cured by intensive chemotherapy.

For patients whose cancers return after intensive chemotherapy or a stem cell transplant, the remaining treatment options are close to none, said Stephan Grupp, M.D., Ph.D., of the Childrens Hospital of Philadelphia (CHOP) and the lead investigator of a trial testing CAR T cells primarily in children with ALL. This treatment may represent a much-needed new option for such patients, he said.

Trials of CAR T cells in adults and children with leukemia and lymphoma have used T cells engineered to target the CD19 antigen, which is present on the surface of nearly all B cells, both normal and cancerous.

In the CHOP trial, which is being conducted in collaboration with researchers from the University of Pennsylvania, all signs of cancer disappeared (a complete response) in 27 of the 30 patients treated in the study, according to findings published October 16 in the New England Journal of Medicine.

Nineteen of the 27 patients with complete responses have remained in remission, the study authors reported, with 15 of these patients receiving no further therapy and 4 patients withdrawing from the trial to receive other therapy.

According to the most recent data from a POB trial that included children with ALL, 14 of 20 patients had a complete response. And of the 12 patients who had no evidence of leukemic cells, called blasts, in their bone marrow after CAR T-cell treatment, 10 have gone on to receive a stem cell transplant and remain cancer free, reported the studys lead investigator, Daniel W. Lee, M.D., also of the POB.

Dr. Crystal Mackall

Our findings strongly suggest that CAR T-cell therapy is a useful bridge to bone marrow transplant for patients who are no longer responding to chemotherapy, Dr. Lee said.

Similar results have been seen in phase I trials of adult patients conducted at MSKCC and NCI.

In findings published in February 2014, 14 of the 16 participants in the MSKCC trial treated to that point had experienced complete responses, which in some cases occurred 2 weeks or sooner after treatment began. Of those patients who were eligible, 7 underwent a stem cell transplant and are still cancer free.

The NCI-led trial of CAR T cells included 15 adult patients, the majority of whom had advanced diffuse large B-cell lymphoma. Most patients in the trial had either complete or partial responses, reported James Kochenderfer, M.D., and his NCI colleagues.

Our data provide the first true glimpse of the potential of this approach in patients with aggressive lymphomas that, until this point, were virtually untreatable, Dr. Kochenderfer said. [NCI Surgery Branch researchers have also reported promising results from one of the first trials testing CAR T cells derived from donors, rather than the patients themselves, to treat leukemia and lymphoma.]

Other findings from the trials have been encouraging, as well. For example, the number of CAR T cells increased dramatically after infusion into patients, as much as 1,000-fold in some individuals. In addition, after infusion, CAR T cells were detected in the central nervous system, a so-called sanctuary site where solitary cancer cells that have evaded chemotherapy or radiation may hide. In two patients in the NCI pediatric trial, the CAR T-cell treatment eradicated cancer that had spread to the central nervous system.

If CAR T cells can persist at these sites, it could help fend off relapses, Dr. Mackall noted.

CAR T-cell therapy can cause several worrisome side effects, perhaps the most troublesome being cytokine-release syndrome.

The infused T cells release cytokines, which are chemical messengers that help the T cells carry out their duties. With cytokine-release syndrome, there is a rapid and massive release of cytokines into the bloodstream, which can lead to dangerously high fevers and precipitous drops in blood pressure.

Cytokine-release syndrome is a common problem in patients treated with CAR T cells. In the POB and CHOP trials, patients with the most extensive disease prior to receiving the CAR T cells were more likely to experience severe cases of cytokine-release syndrome.

For most patients, trial investigators have reported, the side effects are mild enough that they can be managed with standard supportive therapies, including steroids.

The research team at CHOP noticed that patients experiencing severe reactions all had particularly high levels of IL-6, a cytokine that is secreted by T cells and macrophages in response to inflammation. So they turned to two drugs that are approved to treat inflammatory conditions like juvenile arthritis: etanercept (Enbrel) and tocilizumab (Actemra), the latter of which blocks IL-6 activity.

The patients had excellent responses to the treatment, Dr. Grupp said. We believe that [these drugs] will be a major part of toxicity management for these patients.

The other two teams subsequently used tocilizumab in several patients. Dr. Brentjens agreed that both drugs could become a useful way to help manage cytokine-release syndrome because, unlike steroids, they dont appear to affect the infused CAR T cells activity or proliferation.

Even with these encouraging preliminary findings, more research is needed before CAR T-cell therapy becomes a routine option for patients with ALL.

We need to treat more patients and have longer follow-up to really say what the impact of this therapy is [and] to understand its true performance characteristics, Dr. Grupp said.

We need to treat more patients and have longer follow-up to really say what the impact of this therapy is [and] to understand its true performance characteristics.

Dr. Stephan Grupp

Several other trials testing CAR T cells in children and adults are ongoing and, with greater interest and involvement from the pharmaceutical and biotechnology sector, more trials testing CAR T cells are being planned.

Researchers are also studying ways to improve on the positive results obtained to date, including refining the process by which the CAR T cells are produced.

Research groups like Dr. Brentjens are also working to make a superior CAR T cell, including developing a better receptor and identifying better targets.

For example, Dr. Lee and his colleagues at NCI have developed CAR T cells that target the CD22 antigen, which is also present on most B cells, although in smaller quantities than CD19. The CD22-targeted T cells, he believes, could be used in concert with CD19-targeted T cells as a one-two punch in ALL and other B-cell cancers. NCI researchers hope to begin the first clinical trial testing the CD22-targeted CAR T cells in November 2014.

Based on the success thus far, several research groups across the country are turning their attention to developing engineered T cells for other cancers, including solid tumorslike pancreatic and brain cancers.

The stage has now been set for greater progress, Dr. Lee believes.

NCI investigators, for example, now have a platform to plug and play better CARs into that system, without a lot of additional R&D time, he continued. Everything else should now come more rapidly.

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CAR T-Cell Immunotherapy for ALL - National Cancer Institute

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Gene Therapy and Cell Therapy Defined | ASGCT – American …

Tuesday, October 27th, 2015

Gene therapy and cell therapy are overlapping fields of biomedical research with the goals of repairing the direct cause of genetic diseases in the DNA or cellular population, respectively. These powerful strategies are also being focused on modulating specific genes and cell subpopulations in acquired diseases in order to reestablish the normal equilibrium. In many diseases, gene and cell therapy are combined in the development of promising therapies.

In addition, these two fields have helped provide reagents, concepts, and techniques that are elucidating the finer points of gene regulation, stem cell lineage, cell-cell interactions, feedback loops, amplification loops, regenerative capacity, and remodeling.

Gene therapy is defined as a set of strategies that modify the expression of an individuals genes or that correct abnormal genes. Each strategy involves the administration of a specific DNA (or RNA).

Cell therapy is defined as the administration of live whole cells or maturation of a specific cell population in a patient for the treatment of a disease.

Gene therapy: Historically, the discovery of recombinant DNA technology in the 1970s provided the tools to efficiently develop gene therapy. Scientists used these techniques to readily manipulate viral genomes, isolate genes, identify mutations involved in human diseases, characterize and regulate gene expression, and engineer various viral vectors and non-viral vectors. Many vectors, regulatory elements, and means of transfer into animals have been tried. Taken together, the data show that each vector and set of regulatory elements provides specific expression levels and duration of expression. They exhibit an inherent tendency to bind and enter specific types of cells as well as spread into adjacent cells. The effect of the vectors and regulatory elements are able to be reproduced on adjacent genes. The effect also has a predictable survival length in the host. Although the route of administration modulates the immune response to the vector, each vector has a relatively inherent ability, whether low, medium or high, to induce an immune response to the transduced cells and the new gene products.

The development of suitable gene therapy treatments for many genetic diseases and some acquired diseases has encountered many challenges and uncovered new insights into gene interactions and regulation. Further development often involves uncovering basic scientific knowledge of the affected tissues, cells, and genes, as well as redesigning vectors, formulations, and regulatory cassettes for the genes.

While effective long-term treatments for anemias, hemophilia, cystic fibrosis, muscular dystrophy, Gauschers disease, lysosomal storage diseases, cardiovascular diseases, diabetes, and diseases of the bones and joints are elusive today, some success is being observed in the treatment of several types of immunodeficiency diseases, cancer, and eye disorders. Further details on the status of development of gene therapy for specific diseases are summarized here.

Cell therapy: Historically, blood transfusions were the first type of cell therapy and are now considered routine. Bone marrow transplantation has also become a well-established protocol. Bone marrow transplantation is the treatment of choice for many kinds of blood disorders, including anemias, leukemias, lymphomas, and rare immunodeficiency diseases. The key to successful bone marrow transplantation is the identification of a good "immunologically matched" donor, who is usually a close relative, such as a sibling. After finding a good match between the donors and recipients cells, the bone marrow cells of the patient (recipient) are destroyed by chemotherapy or radiation to provide room in the bone marrow for the new cells to reside. After the bone marrow cells from the matched donor are infused, the self-renewing stem cells find their way to the bone marrow and begin to replicate. They also begin to produce cells that mature into the various types of blood cells. Normal numbers of donor-derived blood cells usually appear in the circulation of the patient within a few weeks. Unfortunately, not all patients have a good immunological matched donor. Furthermore, bone marrow grafts may fail to fully repopulate the bone marrow in as many as one third of patients, and the destruction of the host bone marrow can be lethal, particularly in very ill patients. These requirements and risks restrict the utility of bone marrow transplantation to some patients.

Cell therapy is expanding its repertoire of cell types for administration. Cell therapy treatment strategies include isolation and transfer of specific stem cell populations, administration of effector cells, induction of mature cells to become pluripotent cells, and reprogramming of mature cells. Administration of large numbers of effector cells has benefited cancer patients, transplant patients with unresolved infections, and patients with chemically destroyed stem cells in the eye. For example, a few transplant patients cant resolve adenovirus and cytomegalovirus infections. A recent phase I trial administered a large number of T cells that could kill virally-infected cells to these patients. Many of these patients resolved their infections and retained immunity against these viruses. As a second example, chemical exposure can damage or cause atrophy of the limbal epithelial stem cells of the eye. Their death causes pain, light sensitivity, and cloudy vision. Transplantation of limbal epithelial stem cells for treatment of this deficiency is the first cell therapy for ocular diseases in clinical practice.

Several diseases benefit most from treatments that combine the technologies of gene and cell therapy. For example, some patients have a severe combined immunodeficiency disease (SCID) but unfortunately, do not have a suitable donor of bone marrow. Scientists have identified that patients with SCID are deficient in adenosine deaminase gene (ADA-SCID), or the common gamma chain located on the X chromosome (X-linked SCID). Several dozen patients have been treated with a combined gene and cell therapy approach. Each individuals hematopoietic stem cells were treated with a viral vector that expressed a copy of the relevant normal gene. After selection and expansion, these corrected stem cells were returned to the patients. Many patients improved and required less exogenous enzymes. However, some serious adverse events did occur and their incidence is prompting development of theoretically safer vectors and protocols. The combined approach also is pursued in several cancer therapies.

Further information on the progress and status of gene therapy and cell therapy on various diseases is listed here.

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Cell Therapy Ltd

Sunday, October 25th, 2015

Founded in 2009 by Nobel prize winner Professor Sir Martin Evans and Ajan Reginald, former Global Head of Emerging Technologies at Roche, CTL develops life-saving and life altering regenerative medicines. CTLs team of scientists, physicians, and experienced management have discovered and developed a pipeline of world-class regenerative medicines.

Sir Martin Evans' unique expertise in discovering rare stem cells led to CTLs innovative drug discovery engine that can uniquely isolate very rare and potent tissue specific stem cells. This exceptional class of cells is then engineered into unique disease-specific cellular regenerative medicines. Each medicine is disease specific and forms part of CTLs world-class portfolio of four off the shelf blockbuster medicines all scheduled for launch before 2020.

The products in late stage clinical trials include Heartcel which regenerates the damaged heart of adults with coronary artery malformations and children with Kawasaki Disease and Bland White Garland Syndrome. In 2014, Heartcel reported unprecedented heart regeneration clinical trial results and is scheduled to launch in 2018 to treat ~400,000 patients worldwide. Myocardion is in Phase II/III trials and treats mild-moderate heart failure affecting 10 million patients worldwide. Tendoncel is the worlds first topical regenerative medicine, for early intervention of severe tendon injuries, and has completed Phase II trials. It is designed to treat the >1 million severe tendon injuries each year in the US and Europe. Skincel is for skin regeneration, and is due to complete Phase II trials in 2015. It is designed to address ulceration and wrinkles.

CTL combines world-class science and management expertise to bring life-saving regenerative medicines to market.

European Society of Gene and Cell Therapy Congress, 17-20 September 2015, Helsinki,Finland (ESGCT 2015)

4th International Conference and Exhibition on Cell & Gene Therapy, August 10-12, 2015, London (CGT 2015)

The International Society for Stem Cell Research Annual Meeting, 24th-27th June 2015, Stockholm, Sweden (ISSCR 2015)

British Society for Gene and Cell Therapy Annual Conference, 9th-11th June 2015, Strathclyde, Glasgow (BSGCT 2015)

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Cell Therapy Ltd

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Cell Therapy & Regenerative Medicine – University of Utah …

Friday, October 23rd, 2015

About Us

Learn more about Cell Therapy & Regenerative Medicine.

What is a Neurosphere?

CTRM provides services to develop and manufacture novel cellular therapy.

The Cell Therapy and Regenerative Medicine Program (CTRM) at the University of Utah provides the safest, highest quality products for therapeutic use and research. Our goals are to facilitate the availability of cellular and tissue based therapies to patients by bridging efforts in basic research, bioengineering and the medical sciences. As well as assemble the expertise and infrastructure to address the complex regulatory, financial and manufacturing challenges associated with delivering cell and tissue based products to patients.

To support hematopoietic stem cell transplants and to deliver innovative cellular and tissue engineered products to patients by providing comprehensive bench to bedside services that coordinate the efforts of clinicians, researchers, and bioengineers.

Product quality, safety and efficacy; Optimization of resource utilization; Promotion of productive collaborations; Support of innovative products; and Adherence to scientific and ethical excellence.

The Center of Excellence for the state of Utah that translates cutting-edge cell therapy and engineered tissue based research into clinical products that extend and improve the quality of life of individuals suffering from debilitating diseases and injuries.

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Mississippi Stem Cell Treatment Center – Ocean Springs, MS

Sunday, October 4th, 2015

As a national pioneer of innovative medicine, Mississippi Stem Cell Treatment Centers motto Excellence with a Human Touch, is at the forefront of what we do. Located in the city of Ocean Springs on the Mississippi Gulf Coast, we provide treatment to promote healing and tissue generation to those suffering from autoimmune, degenerative, inflammatory and ischemic conditions. Our team is highly committed to alleviating your symptoms and enhancing your functionality, quality of life, and wellbeing.

We employ a method called Stromal Vascular Fraction deployment (SVF). SVF relies on individual patient stem cells and growth factors, and helps accelerate healing and tissue regeneration. The SVF we collect from patients fat tissue is given back to the individual through the deployment process. SVF is an innovative product that can be used to regenerate different types of tissue throughout the body.

Mississippi Stem Cell Treatment Center is an affiliate of the Cell Surgical Network of CA. Our center meets all FDA guidelines for treating patients using their own tissue for therapy. We provide same-day harvesting and treatment in a state-of-the-art environment, which facilitates a faster recovery.

We provide treatment for anyone suffering in the following areas:

At Mississippi Stem Cell Treatment Center, we offer stem cell center treatments for autoimmune disease, as well as stem cell center treatment for people suffering from other degenerative diseases. For more information on our innovative technology, browse our website for a wealth of information on stem cells, or contact us so we can discuss your individual candidate profile.

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Regenerative Medicine and Stem cell based Cell therapies …

Sunday, October 4th, 2015

Information contained on this page is provided by an independent third-party content provider. WorldNow and this Station make no warranties or representations in connection therewith. If you have any questions or comments about this page please contact pressreleases@worldnow.com.

SOURCE Reportlinker

NEW YORK, Oct. 1, 2015 /PRNewswire/ -- Innovative Therapies for treating diseases are being sought after with fresh vigor as new targets, approaches and biology is discovered. Improved health care, nutrition and preventive medicine in the last few decades have all helped in increasing the life expectancy WW. However, this has not translated into any reduction in the incidence or prevalence of chronic or critical illnesses! On the contrary the incidence of chronic diseases like diabetes, obesity, arthritis etc. as well as cancer and the maladies associated with aging (dementia, Alzheimer's etc.) are on the rise!. Consequently the pharma industry continues to grow and is projected to

achieve sales in excess of trillion dollar mark by 2020 By the next decade, one field which is poised to bring a paradigm change in the way diseases are treated is the Stem cell therapy/Regenerative Medicine space. The number of companies and products in the clinic have reached a critical mass warranting a close watch for those interested in keeping pace with the development of new medicines.

Regenerative Medicine and Stem cell based Cell therapies-Drugs of the Future Offering Hope for Cure

EXECUTIVE SUMMARY

- INTRODUCTION

- Tough Choice- "Autologous vs. Allogenic " Therapies

- REGULATORY GUIDELINES

- Marketed Cell based/Stem Cell Products

- Progress and Challenges

- Progress in Specific Therapy Areas

- SELECT UPCOMING MILESTONES IN REGENERATIVE MEDICINE/STEM

CELL FOCUSED COMPANIES (2015-16)

- Appendix

Read the full report: http://www.reportlinker.com/p02629094-summary/view-report.html

About Reportlinker ReportLinker is an award-winning market research solution that finds, filters and organizes the latest industry data so you get all the market research you need - instantly, in one place.

http://www.reportlinker.com

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To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/regenerative-medicine-and-stem-cell-based-cell-therapies-drugs-of-the-future-offering-hope-for-cure-300153074.html

2015 PR Newswire. All Rights Reserved.

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Research – Stem Cell Biology and Regenerative Medicine …

Friday, September 25th, 2015

Every one of us completely regenerates our own skin every 7 days. A cut heals itself and disappears in a week or two. Every single cell in our skeleton is replaced every 7 years.

The future of medicine lies in understanding how the body creates itself out of a single cell and the mechanisms by which it renews itself throughout life.

When we achieve this goal, we will be able to replace damaged tissues and help the body regenerate itself, potentially curing or easing the suffering of those afflicted by disorders like heart disease, Alzheimers, Parkinsons, diabetes, spinal cord injury and cancer.

Research at the institute leverages Stanfords many strengths in a way that promotes that goal. The institute brings together experts from a wide range of scientific and medical fields to create a fertile, multidisciplinary research environment.

There are four major research areas of emphasis at the institute:

Theres no way to know, beforehand, which particular avenue of stem cell research will most expediently yield a successful treatment or cure. Therefore, we need to vigorously pursue a broad number of promising leads concurrently.

--Philip A. Pizzo, MD Carl and Elizabeth Naumann Professor Dean, Stanford University School of Medicine

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Stem Cell Treatment May Help Ease Osteoarthritis Pain …

Wednesday, September 16th, 2015

Last year, Patricia Beals was told she'd need a double knee replacement to repair her severely arthritic knees or she'd probably spend the rest of her life in a wheelchair.

Hoping to avoid surgery, Beals, 72, opted instead for an experimental treatment that involved harvesting bone marrow stem cells from her hip, concentrating the cells in a centrifuge and injecting them back into her damaged joints.

"Almost from the moment I got up from the table, I was able to throw away my cane," Beals says. "Now I'm biking and hiking like a 30-year-old."

A handful of doctors around the country are administering treatments like the one Beals received to stop or even reverse the ravages of osteoarthritis. Stem cells are the only cells in the body able to morph into other types of specialized cells. When the patient's own stem cells are injected into a damaged joint, they appear to transform into chondrocytes, the cells that go on to produce fresh cartilage. They also seem to amplify the body's own natural repair efforts by accelerating healing, reducing inflammation, and preventing scarring and loss of function.

Christopher J. Centeno, M.D., the rehab medicine specialist who performed Beals' procedure, says the results he sees from stem cell therapy are remarkable. Of the more-than-200 patients his Bloomfield, Colo., clinic treated over a two-year period, he says, "two thirds of them reported greater than 50 percent relief and about 40 percent reported more than 75 percent relief one to two years afterward."

According to Centeno, knees respond better to the treatment than hips. Only eight percent of his knee patients opted for a total knee replacement two years after receiving a stem cell injection. The complete results from his clinical observations will be published in a major orthopedic journal later this year.

The Pros and Cons

The biggest advantage stem cell injections seem to offer over more invasive arthritis remedies is a quicker, easier recovery. The procedure is done on an outpatient basis and the majority of patients are up and moving within 24 hours. Most wear a brace for several weeks but still can get around. Many are even able to do some gentle stationary cycling by the end of the first week.

There are also fewer complications. A friend who had knee replacement surgery the same day Beals had her treatment developed life-threatening blood clots and couldn't walk for weeks afterwards. Six months out, she still hasn't made a full recovery.

Most surgeries don't go so awry, but still: Beals just returned from a week-long cycling trip where she covered 20 to 40 miles per day without so much as a tweak of pain.

As for risks, Centeno maintains they are virtually nonexistent.

"Because the stem cells come from your own body, there's little chance of infection or rejection," he says.

Not all medical experts are quite so enthusiastic, however. Dr. Tom Einhorn, chairman of the department of orthopedic surgery at Boston University, conducts research with stem cells but does not use them to treat arthritic patients. He thinks the idea is interesting but the science is not there yet.

"We need to have animal studies and analyze what's really happening under the microscope. Then, and only then, can you start doing this with patients," he says.

The few studies completed to date have examined how stem cells heal traumatic injuries rather than degenerative conditions such as arthritis. Results have been promising but, as Einhorn points out, the required repair mechanisms in each circumstance are very different.

Another downside is cost: The injections aren't approved by the FDA, which means they aren't covered by insurance. At $4,000 a pop -- all out of pocket -- they certainly aren't cheap, and many patients require more than one shot.

Ironically, one thing driving up the price is FDA involvement. Two years ago, the agency stepped in and stopped physicians from intensifying stem cells in the lab for several days before putting them back into the patient. This means all procedures must be done on the same day, no stem cells may be preserved and many of the more expensive aspects of the treatment must be repeated each time.

Centeno says same day treatments often aren't as effective, either.

But despite the sky-high price tag and lack of evidence, patients like Beals believe the treatment is nothing short of a miracle. She advises anyone who is a candidate for joint replacement to consider stem cells first.

"Open your mind up and step into it," she says. "Do it. It's so effective. It's the future and it works."

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Knoepfler Lab Stem Cell Blog | Building innovative …

Friday, September 11th, 2015

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Its a shame that National Geographic has become part of a corporate empire that is not always consistent, to put it nicely, with data-based reality. Can NatGeo maintain its credibility and impact, when it is owned by a climate change denier (quoted for example as dissing folks as extreme greenies) who also has other verynon-scientificpriorities?

Theres been an increasing amount of discussion of the technology that could produce GM humans. This dialogue includes the new Hinxton Statement (my take on that here) and George Churchs quoted that Hinxton (which BTW did not call for a moratorium of any kind) was being too cautious nonetheless. Church is quoted:

seems weak on addressing why we should single out genome editing relative to other medicines that are potentially dangerous

Should we push pause, stop, or fast-forward on human genetic modification? asks Lisa Ikemoto.Is there a rewind or edit button too?

The NEJM published a new piece on stem cell clinics run amok and the lack of an effective FDA response. Sounds awfully familiar including the use of Wild West in the title, right? My gripe with these authors is that they didnt give credit where credit is due to those of us on the front lines of this battle and in particular to social media-based efforts to promote evidence-based medicine in the stem cell arena. Still, their message was on target.

Are men more likely to commit large-scale scientific fraud? Check out RetractionWatchs leaderboard.Of course the sheer number of retractions does not take into account the impact of any one or two given retractions that had a disproportionate toxic effect like the STAP pubs. Maybe another calculation to do is the # of citations to a retracted paper.

DrugMonkey talks about perceived scientific backstabbing.

The international stem cell policy and ethics think tank, the Hinxton Group, weighed in yesterday on heritable human genetic modification with a new policy statement.

The Hinxton statement is in many ways in agreement with the Baltimore, et al. Nature paper proposing a prudent path forward for human germline genetic modification, which came out of the Napa Meeting earlier this year.

However, while several of the Napa authors have now thrown their public support behind a clinical pause or moratorium on heritable human modification (e.g. Jennifer Doudnaas well asDavid Baltimore and Paul Berg in a later piece in the WSJ), Hinxton didnt explicitlyaddress either positively or negatively the question of a moratorium.

My initial reading of the Hinxton statement is that I mostly agree with it. In my own proposed ABCD planon human germline modification from earlier this year, however, I included at least a temporary clinical moratorium.

I also would have appreciated a more detailed risk-benefit analysis in the Hinxton statement. For instance, I didnt see a discussion of specific possible risks in their statement. Via myown risk-benefit analysis, I come to the conclusion that on the whole a temporary clinical moratorium has the potential for far more benefit than harm.

What would be the specific, possible benefits of a moratorium?

If the scientific community has united behind a moratorium on clinical use not only will that discourage rogue or potentially ill-advised stabs at clinical use, but also if a few such dangerous efforts proceed anyway (which is fairly likely) and come to public light, these unfortunate events will be placed in the appropriate context of the scientific community having a moratorium in place. Therefore, a moratorium both discourages premature and dangerous clinical use as well as putting potential future human gene editing clinical mishaps into the proper context for the pubic.

Another potential benefit of a moratorium is that it could discourage lawmakers from passing reactionary, overly restrictive legislation that bans both clinical applications and important in vitro research. It would give the politicians and the public the right sense that the scientific community is handling this situation with appropriate caution. If you dont think that a law on human germline modification is likely in the US, consider that conservative lawmakers have already proposed such a law be included as part of the pending appropriations bill and Congress a few months ago held a hearing on germline human modification.

Other benefits of a moratorium include that it would a) demonstrate to the public that the research community is capable of reaching consensus aboutimportant ethical issues and b) increase accountability within the research community. Any rogue researchers or clinicians who would violate the moratorium, even if it were not illegal for them to do so, would at least be subject to the disapproval and possible sanction of their professional peers or institutions. Without a moratorium in place, it is far less likely there would be these kinds of consequences.

What about risks to a clinical moratorium?The primary possible risk of a clinical moratorium is that it could, should human heritable genetic modification someday down the road be viewed as a wise course to pursue directly, impede clinical translation. This warrants discussion, but in my view the risk here is somewhat reduced by the possibility that continuing basic research develops a compelling case that a blanket clinical moratorium might no longer be needed.

The other risk here is that amoratorium on clinical use also might in theory discourage some potentially valuable pre-clinical research as well. In other words, some researchers may adopt the mindset that if they cannot get to their ultimate goal of making clinical impact, why do the preclinical studies? I expect that many researchers would instead go ahead and do the preclinical work with the expectation that a clinical moratorium could be lifted and in fact their own preclinical work might help build a case for moving beyond a moratorium.

I agreestrongly with Hinxton on the need for continuation of basic science on CRISPR and other gene editing technologies limited to the lab. In my view, we should have a nuanced policy though, whereby we support continuation of gene editing research in human cells and even in some cases human embryos in the lab under specific conditions (see again my ABCD plan for details), but in whichwe also put an unambiguous hold onclinical applications at this time.

In the absence of a framework that includes a clinical moratorium, we probably do not have the luxury of a reasonably long time frame (e.g. measured in a few years) for open discussionto sort things out carefully. To be clear, open and diverse discussion is crucial, but we just do not have a whole lot of time to do it as things stand today. Why? In the mean time absent a moratorium, I believe that some will go ahead and do clinical experiments on human germline editing. This would not only put individual research subjects at risk, but also pose dangers in terms of public trust and support to the wider scientific community. In a relatively permissive environment lacking a clinical moratorium, one or two instances of rogue researchers clinically using gene editing in a heritable manner could end up leading to a backlash in which even in vitro gene editing research is stymied.

Stemcentrx scientists working with targeted molecules that can kill some types of lung cancer. MIT Tech Review Image.

A stem cell biotech in the news this week was one thathad mostly flown under the radar previously.

Stemcentrx hasa focus on killing cancer stem cells as a novel approach to treating cancer. Antonio Regalado had a nice articleyesterday on the company. He reports that Stemcentrx has around a half a billion in funding. It is valued in the billions. These are very unusual figures for a stem cell biotech.

Stemcentrx isdeveloping novel cancer therapeutics such as antibodies that target cancer stem cells. Their development pipeline at least in part uses a model of serial xenograft tumor transplantation in mice.Cancer stem cells are also sometimes called tumor initiating cells (TIC). As a cancer stem cell researcher myself, I find Stemcentrx intriguing.

The company published an encouraging bit of preclinical data recently in Science Translational Medicinewith a team of authors including leading company scientist, Scott Dylla. In this paper the team presented evidence that they have a product in the form of a loaded antibody (conjugated to a toxin) against a molecule called DLL3 important to TIC biological function and survival. DLL3 is part of the Notch signaling pathway. Stay tuned tomorrow for my interview with Dr. Dylla.

They showed that this anti-DLL3 antibody,SC16LD6.5, exhibited anti-tumor activities in xenograft models of pulmonary neuroendocrine tumors such as small cell lung cancer. The company also has a clinical trial ongoing but not currently recruiting using this drug, and they have another trial for ovarian cancer based on antibody targeting as well.

SC16LD6.5 also exhibited some degree of toxicity in rats and a non-human primate model so thats a possible issue moving forward, but the toxic effects were at least partially reversible and when youre dealing with a deadly disease some toxicity for treatment is kind of to be expected.

Can Stemcentrx survive and hopefully even thrive as a company selling products that kill cancer stem cells? Well have a clearer picture on this in a few years, but in general biotechs of this type in this arena have a high failure rate. We need to keep in mind the long, sobering path ahead between these kinds of preclinical result and getting an approved drug to patients.

At the same time, this team has the money and talent to potentially succeed, and again, theres that half a billion in funding, which all by itself makes this stem cell biotech noordinary company. Theres another unique thing going on here: famed tech investor Peter Thiel is one of the major funders of the company.

Those of us in the cancer stem cell field have long been engaged in the debate overwhether these special cells exist in specific solid tumors and their functions in tumorigenesis. I believe they are present and important in some, but not all of such tumors. The controversial nature of TICs in lung cancer specifically makes SC16LD6.5 a high-risk, high reward kind ofproduct.

More weapons against lung cancer will be of coursea good thing and targeting cancer stem cells is an innovative approach. The company isrecruiting for many positions including scientists so if you are interested take a look.

I hope Stemcentrx succeeds and I look forward to reading more of their work as the years go by.

The winner of the inaugural Ogawa-Yamanaka Prize is Dr. Masayo Takahashi, MD, PhD.

According to the Gladstone Institutepress release, Dr. Takahashi was awarded the prize for her trailblazing work leading the first clinical trial to use induced pluripotent stem (iPS) cells in humans.

The prize, including a $150,000 cash award, will be given at a ceremony next week at the Gladstone on September 16. If you are interested in listening in, you can register for the webcast here.

Dr. Takahashi started the first ever human clinical study using iPS cells, which is focused on treating of macular degeneration using retinal pigmented epithelial cells derived from human iPS cells.

Congratulations to Dr. Takahashi for the great and well-deserved honor of the Ogawa-Yamanaka Prize.

As readers of this blog likely recall, Dr. Takahashi received our blogsStem Cell Person of the Year Award last year in honor of her pioneering work and that included a $2,000 prize.

Otherpast winners of our Stem Cell Person of the Year Award have gone on to get additional awards too.

The 2013 Stem Cell Person of the Year, Dr. Elena Cattaneo, went on to win the ISSCR Public Service Award in 2014 along with colleagues.

And our 2012 Stem Cell Person of the Year Award winner, stellar patient advocateRoman Reed, went on in 2013 to receive the GPI Stem Cell Inspiration Award.

The more we can recognize the pioneers and outside-the-box thinkers in the stem cell field, the better.

I recently ran a poll on my blog about how the FDA is doing on handling stem cell clinics.

There is substantial debate in the stem cell arena about how the FDA handles stem cell clinics ranging from the view that the agency is far too strict to excessively lenient.

The results of the poll reflect a great deal of dissatisfaction with the job that the FDA is doing on stem cell clinics.

Only 9% of respondents felt that the FDA is currently do things just about right.

While the top 2 answers were polar extremes, by a large margin the top answer was that the FDA was much too lenient.

Although Internet polls of this kind are not scientific, they can reflect sentiments of a community.

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Cell culture – Wikipedia, the free encyclopedia

Monday, September 7th, 2015

Cell culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. In practice, the term "cell culture" now refers to the culturing of cells derived from multicellular eukaryotes, especially animal cells, in contrast with other types of culture that also grow cells, such as plant tissue culture, fungal culture, and microbiological culture (of microbes). The historical development and methods of cell culture are closely interrelated to those of tissue culture and organ culture. Viral culture is also related, with cells as hosts for the viruses.

The laboratory technique of maintaining live cell lines (a population of cells descended from a single cell and containing the same genetic makeup) separated from their original tissue source became more robust in the middle 20th century.[1][2]

The 19th-century English physiologist Sydney Ringer developed salt solutions containing the chlorides of sodium, potassium, calcium and magnesium suitable for maintaining the beating of an isolated animal heart outside of the body.[3] In 1885, Wilhelm Roux removed a portion of the medullary plate of an embryonic chicken and maintained it in a warm saline solution for several days, establishing the principle of tissue culture.[4]Ross Granville Harrison, working at Johns Hopkins Medical School and then at Yale University, published results of his experiments from 1907 to 1910, establishing the methodology of tissue culture.[5]

Cell culture techniques were advanced significantly in the 1940s and 1950s to support research in virology. Growing viruses in cell cultures allowed preparation of purified viruses for the manufacture of vaccines. The injectable polio vaccine developed by Jonas Salk was one of the first products mass-produced using cell culture techniques. This vaccine was made possible by the cell culture research of John Franklin Enders, Thomas Huckle Weller, and Frederick Chapman Robbins, who were awarded a Nobel Prize for their discovery of a method of growing the virus in monkey kidney cell cultures.

Cells can be isolated from tissues for ex vivo culture in several ways. Cells can be easily purified from blood; however, only the white cells are capable of growth in culture. Mononuclear cells can be released from soft tissues by enzymatic digestion with enzymes such as collagenase, trypsin, or pronase, which break down the extracellular matrix. Alternatively, pieces of tissue can be placed in growth media, and the cells that grow out are available for culture. This method is known as explant culture.

Cells that are cultured directly from a subject are known as primary cells. With the exception of some derived from tumors, most primary cell cultures have limited lifespan.

An established or immortalized cell line has acquired the ability to proliferate indefinitely either through random mutation or deliberate modification, such as artificial expression of the telomerase gene. Numerous cell lines are well established as representative of particular cell types.

For the majority of isolated primary cells, they undergo the process of senescence and stop dividing after a certain number of population doublings while generally retaining their viability (described as the Hayflick limit).

Cells are grown and maintained at an appropriate temperature and gas mixture (typically, 37C, 5% CO2 for mammalian cells) in a cell incubator. Culture conditions vary widely for each cell type, and variation of conditions for a particular cell type can result in different phenotypes.

Aside from temperature and gas mixture, the most commonly varied factor in culture systems is the cell growth medium. Recipes for growth media can vary in pH, glucose concentration, growth factors, and the presence of other nutrients. The growth factors used to supplement media are often derived from the serum of animal blood, such as fetal bovine serum (FBS), bovine calf serum, equine serum, and porcine serum. One complication of these blood-derived ingredients is the potential for contamination of the culture with viruses or prions, particularly in medical biotechnology applications. Current practice is to minimize or eliminate the use of these ingredients wherever possible and use human platelet lysate (hPL). This eliminates the worry of cross-species contamination when using FBS with human cells. hPL has emerged as a safe and reliable alternative as a direct replacement for FBS or other animal serum. In addition, chemically defined media can be used to eliminate any serum trace (human or animal), but this cannot always be accomplished with different cell types. Alternative strategies involve sourcing the animal blood from countries with minimum BSE/TSE risk, such as The United States, Australia and New Zealand,[6] and using purified nutrient concentrates derived from serum in place of whole animal serum for cell culture.[7]

Plating density (number of cells per volume of culture medium) plays a critical role for some cell types. For example, a lower plating density makes granulosa cells exhibit estrogen production, while a higher plating density makes them appear as progesterone-producing theca lutein cells.[8]

Cells can be grown either in suspension or adherent cultures. Some cells naturally live in suspension, without being attached to a surface, such as cells that exist in the bloodstream. There are also cell lines that have been modified to be able to survive in suspension cultures so they can be grown to a higher density than adherent conditions would allow. Adherent cells require a surface, such as tissue culture plastic or microcarrier, which may be coated with extracellular matrix (such as collagen and laminin) components to increase adhesion properties and provide other signals needed for growth and differentiation. Most cells derived from solid tissues are adherent. Another type of adherent culture is organotypic culture, which involves growing cells in a three-dimensional (3-D) environment as opposed to two-dimensional culture dishes. This 3D culture system is biochemically and physiologically more similar to in vivo tissue, but is technically challenging to maintain because of many factors (e.g. diffusion).

Cell line cross-contamination can be a problem for scientists working with cultured cells.[9] Studies suggest anywhere from 1520% of the time, cells used in experiments have been misidentified or contaminated with another cell line.[10][11][12] Problems with cell line cross-contamination have even been detected in lines from the NCI-60 panel, which are used routinely for drug-screening studies.[13][14] Major cell line repositories, including the American Type Culture Collection (ATCC), the European Collection of Cell Cultures (ECACC) and the German Collection of Microorganisms and Cell Cultures (DSMZ), have received cell line submissions from researchers that were misidentified by them.[13][15] Such contamination poses a problem for the quality of research produced using cell culture lines, and the major repositories are now authenticating all cell line submissions.[16] ATCC uses short tandem repeat (STR) DNA fingerprinting to authenticate its cell lines.[17]

To address this problem of cell line cross-contamination, researchers are encouraged to authenticate their cell lines at an early passage to establish the identity of the cell line. Authentication should be repeated before freezing cell line stocks, every two months during active culturing and before any publication of research data generated using the cell lines. Many methods are used to identify cell lines, including isoenzyme analysis, human lymphocyte antigen (HLA) typing, chromosomal analysis, karyotyping, morphology and STR analysis.[17]

One significant cell-line cross contaminant is the immortal HeLa cell line.

As cells generally continue to divide in culture, they generally grow to fill the available area or volume. This can generate several issues:

Among the common manipulations carried out on culture cells are media changes, passaging cells, and transfecting cells. These are generally performed using tissue culture methods that rely on aseptic technique. Aseptic technique aims to avoid contamination with bacteria, yeast, or other cell lines. Manipulations are typically carried out in a biosafety hood or laminar flow cabinet to exclude contaminating micro-organisms. Antibiotics (e.g. penicillin and streptomycin) and antifungals (e.g.amphotericin B) can also be added to the growth media.

As cells undergo metabolic processes, acid is produced and the pH decreases. Often, a pH indicator is added to the medium to measure nutrient depletion.

In the case of adherent cultures, the media can be removed directly by aspiration, and then is replaced. Media changes in non-adherent cultures involve centrifuging the culture and resuspending the cells in fresh media.

Passaging (also known as subculture or splitting cells) involves transferring a small number of cells into a new vessel. Cells can be cultured for a longer time if they are split regularly, as it avoids the senescence associated with prolonged high cell density. Suspension cultures are easily passaged with a small amount of culture containing a few cells diluted in a larger volume of fresh media. For adherent cultures, cells first need to be detached; this is commonly done with a mixture of trypsin-EDTA; however, other enzyme mixes are now available for this purpose. A small number of detached cells can then be used to seed a new culture. Some cell cultures, such as RAW cells are mechanically scraped from the surface of their vessel with rubber scrapers.

Another common method for manipulating cells involves the introduction of foreign DNA by transfection. This is often performed to cause cells to express a protein of interest. More recently, the transfection of RNAi constructs have been realized as a convenient mechanism for suppressing the expression of a particular gene/protein. DNA can also be inserted into cells using viruses, in methods referred to as transduction, infection or transformation. Viruses, as parasitic agents, are well suited to introducing DNA into cells, as this is a part of their normal course of reproduction.

Cell lines that originate with humans have been somewhat controversial in bioethics, as they may outlive their parent organism and later be used in the discovery of lucrative medical treatments. In the pioneering decision in this area, the Supreme Court of California held in Moore v. Regents of the University of California that human patients have no property rights in cell lines derived from organs removed with their consent.[19]

It is possible to fuse normal cells with an immortalised cell line. This method is used to produce monoclonal antibodies. In brief, lymphocytes isolated from the spleen (or possibly blood) of an immunised animal are combined with an immortal myeloma cell line (B cell lineage) to produce a hybridoma which has the antibody specificity of the primary lymphocyte and the immortality of the myeloma. Selective growth medium (HA or HAT) is used to select against unfused myeloma cells; primary lymphoctyes die quickly in culture and only the fused cells survive. These are screened for production of the required antibody, generally in pools to start with and then after single cloning.

A cell strain is derived either from a primary culture or a cell line by the selection or cloning of cells having specific properties or characteristics which must be defined. Cell strains are cells that have been adapted to culture but, unlike cell lines, have a finite division potential. Non-immortalized cells stop dividing after 40 to 60 population doublings[20] and, after this, they lose their ability to proliferate (a genetically determined event known as senescence).[21]

Mass culture of animal cell lines is fundamental to the manufacture of viral vaccines and other products of biotechnology.

Biological products produced by recombinant DNA (rDNA) technology in animal cell cultures include enzymes, synthetic hormones, immunobiologicals (monoclonal antibodies, interleukins, lymphokines), and anticancer agents. Although many simpler proteins can be produced using rDNA in bacterial cultures, more complex proteins that are glycosylated (carbohydrate-modified) currently must be made in animal cells. An important example of such a complex protein is the hormone erythropoietin. The cost of growing mammalian cell cultures is high, so research is underway to produce such complex proteins in insect cells or in higher plants, use of single embryonic cell and somatic embryos as a source for direct gene transfer via particle bombardment, transit gene expression and confocal microscopy observation is one of its applications. It also offers to confirm single cell origin of somatic embryos and the asymmetry of the first cell division, which starts the process.

Research in tissue engineering, stem cells and molecular biology primarily involves cultures of cells on flat plastic dishes. This technique is known as two-dimensional (2D) cell culture, and was first developed by Wilhelm Roux who, in 1885, removed a portion of the medullary plate of an embryonic chicken and maintained it in warm saline for several days on a flat glass plate. From the advance of polymer technology arose today's standard plastic dish for 2D cell culture, commonly known as the Petri dish. Julius Richard Petri, a German bacteriologist, is generally credited with this invention while working as an assistant to Robert Koch. Various researchers today also utilize culturing laboratory flasks, conicals, and even disposable bags like those used in single-use bioreactors.

Aside from Petri dishes, scientists have long been growing cells within biologically derived matrices such as collagen or fibrin, and more recently, on synthetic hydrogels such as polyacrylamide or PEG. They do this in order to elicit phenotypes that are not expressed on conventionally rigid substrates. There is growing interest in controlling matrix stiffness,[22] a concept that has led to discoveries in fields such as:

Cell culture in three dimensions has been touted as "Biology's New Dimension".[37] Nevertheless, the practice of cell culture remains based on varying combinations of single or multiple cell structures in 2D.[38] That being said, there is an increase in use of 3D cell cultures in research areas including drug discovery, cancer biology, regenerative medicine and basic life science research.[39] There are a variety of platforms used to facilitate the growth of three-dimensional cellular structures such as nanoparticle facilitated magnetic levitation,[40] gel matrices scaffolds, and hanging drop plates.[41]

3D Cell Culturing by Magnetic Levitation method (MLM) is the application of growing 3D tissue by inducing cells treated with magnetic nanoparticle assemblies in spatially varying magnetic fields using neodymium magnetic drivers and promoting cell to cell interactions by levitating the cells up to the air/liquid interface of a standard petri dish. The magnetic nanoparticle assemblies consist of magnetic iron oxide nanoparticles, gold nanoparticles, and the polymer polylysine. 3D cell culturing is scalable, with the capability for culturing 500 cells to millions of cells or from single dish to high-throughput low volume systems.

Cell culture is a fundamental component of tissue culture and tissue engineering, as it establishes the basics of growing and maintaining cells in vitro. The major application of human cell culture is in stem cell industry, where mesenchymal stem cells can be cultured and cryopreserved for future use. Tissue engineering potentially offers dramatic improvements in low cost medical care for hundreds of thousands of patients annually.

Vaccines for polio, measles, mumps, rubella, and chickenpox are currently made in cell cultures. Due to the H5N1 pandemic threat, research into using cell culture for influenza vaccines is being funded by the United States government. Novel ideas in the field include recombinant DNA-based vaccines, such as one made using human adenovirus (a common cold virus) as a vector,[42][43] and novel adjuvants.[44]

Plant cell cultures are typically grown as cell suspension cultures in a liquid medium or as callus cultures on a solid medium. The culturing of undifferentiated plant cells and calli requires the proper balance of the plant growth hormones auxin and cytokinin.

Cells derived from Drosophila melanogaster (most prominently, Schneider 2 cells) can be used for experiments which may be hard to do on live flies or larvae, such as biochemical studies or studies using siRNA. Cell lines derived from the army worm Spodoptera frugiperda, including Sf9 and Sf21, and from the cabbage looper Trichoplusia ni, High Five cells, are commonly used for expression of recombinant proteins using baculovirus.

For bacteria and yeasts, small quantities of cells are usually grown on a solid support that contains nutrients embedded in it, usually a gel such as agar, while large-scale cultures are grown with the cells suspended in a nutrient broth.

The culture of viruses requires the culture of cells of mammalian, plant, fungal or bacterial origin as hosts for the growth and replication of the virus. Whole wild type viruses, recombinant viruses or viral products may be generated in cell types other than their natural hosts under the right conditions. Depending on the species of the virus, infection and viral replication may result in host cell lysis and formation of a viral plaque.

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Induced pluripotent stem cell – Wikipedia, the free …

Saturday, August 22nd, 2015

Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells. The iPSC technology was pioneered by Shinya Yamanakas lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells.[1] He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent." [2]

Pluripotent stem cells hold great promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

The most well-known type of pluripotent stem cell is the embryonic stem cell. However, since the generation of embryonic stem cells involves destruction (or at least manipulation) [3] of the pre-implantation stage embryo, there has been much controversy surrounding their use. Further, because embryonic stem cells can only be derived from embryos, it has so far not been feasible to create patient-matched embryonic stem cell lines.

Since iPSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line. These unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection. While the iPSC technology has not yet advanced to a stage where therapeutic transplants have been deemed safe, iPSCs are readily being used in personalized drug discovery efforts and understanding the patient-specific basis of disease.[citation needed]

Depending on the methods used, reprogramming of adult cells to obtain iPSCs may pose significant risks that could limit their use in humans. For example, if viruses are used to genomically alter the cells, the expression of oncogenes (cancer-causing genes) may potentially be triggered. In February 2008, scientists announced the discovery of a technique that could remove oncogenes after the induction of pluripotency, thereby increasing the potential use of iPS cells in human diseases.[4] In April 2009, it was demonstrated that generation of iPS cells is possible without any genetic alteration of the adult cell: a repeated treatment of the cells with certain proteins channeled into the cells via poly-arginine anchors was sufficient to induce pluripotency.[5] The acronym given for those iPSCs is piPSCs (protein-induced pluripotent stem cells).

iPSCs are typically derived by introducing a specific set of pluripotency-associated genes, or reprogramming factors, into a given cell type. The original set of reprogramming factors (also dubbed Yamanaka factors) are the genes Oct4 (Pou5f1), Sox2, cMyc, and Klf4. While this combination is most conventional in producing iPSCs, each of the factors can be functionally replaced by related transcription factors, miRNAs, small molecules, or even non-related genes such as lineage specifiers.

iPSC derivation is typically a slow and inefficient process, taking 12 weeks for mouse cells and 34 weeks for human cells, with efficiencies around 0.01%0.1%. However, considerable advances have been made in improving the efficiency and the time it takes to obtain iPSCs. Upon introduction of reprogramming factors, cells begin to form colonies that resemble pluripotent stem cells, which can be isolated based on their morphology, conditions that select for their growth, or through expression of surface markers or reporter genes.

Induced pluripotent stem cells were first generated by Shinya Yamanaka's team at Kyoto University, Japan, in 2006.[1] Their hypothesis was that genes important to embryonic stem cell function might be able to induce an embryonic state in adult cells. They began by choosing twenty-four genes that were previously identified as important in embryonic stem cells, and used retroviruses to deliver these genes to fibroblasts from mice. The mouse fibroblasts were engineered so that any cells that reactivated the ESC-specific gene, Fbx15, could be isolated using antibiotic selection.

Upon delivery of all twenty-four factors, colonies emerged that had reactivated the Fbx15 reporter, resembled ESCs, and could propagate indefinitely. They then narrowed their candidates by removing one factor at a time from the pool of twenty-four. By this process, they identified four factors, Oct4, Sox2, cMyc, and Klf4, which as a group were both necessary and sufficient to obtain ESC-like colonies under selection for reactivation of Fbx15.

Similar to ESCs, these first-generation iPSCs showed unlimited self-renewal and demonstrated pluripotency by contributing to lineages from all three germ layers in the context of embryoid bodies, teratomas, fetal chimeras. However, the molecular makeup of these cells, including gene expression and epigenetic marks, was somewhere between that of a fibroblast and an ESC, and the cells also failed to produce viable chimeras when injected into developing embryos.

In June 2007, the same group published a breakthrough study along with two other independent research groups from Harvard, MIT, and the University of California, Los Angeles, showing successful reprogramming of mouse fibroblasts into iPS cells. Unlike the first generation of iPS cells, these cells could produce viable chimeric mice and could contribute to the germline, the 'gold standard' for pluripotent stem cells. These cells were derived from mouse fibroblasts by retroviral-mediated expression of the same four transcription factors (Oct4, Sox2, cMyc, Klf4), but the researchers used a different marker to select for pluripotent cells. Instead of Fbx15, they used Nanog, a gene that is functionally important in ESCs. By using this different strategy, the researchers were able to create iPS cells that were more similar to ESCs than the first generation of iPS cells, and independently proved that it was possible to create iPS cells that are functionally identical to ESCs.[6][7][8][9]

Unfortunately, two of the four genes used (namely, c-Myc and KLF4) are oncogenic, and 20% of the chimeric mice developed cancer. In a later study, Yamanaka reported that one can create iPSCs even without c-Myc. The process takes longer and is not as efficient, but the resulting chimeras didn't develop cancer.[10]

Induced pluripotent cells have been made from adult stomach, liver, skin cells, blood cells, prostate cells and urinary tract cells.[11]

In November 2007, a milestone was achieved[12][13] by creating iPSCs from adult human cells; two independent research teams' studies were released one in Science by James Thomson at University of WisconsinMadison[14] and another in Cell by Shinya Yamanaka and colleagues at Kyoto University, Japan.[15] With the same principle used earlier in mouse models, Yamanaka had successfully transformed human fibroblasts into pluripotent stem cells using the same four pivotal genes: Oct3/4, Sox2, Klf4, and c-Myc with a retroviral system. Thomson and colleagues used OCT4, SOX2, NANOG, and a different gene LIN28 using a lentiviral system.

On 8 November 2012, researchers from Austria, Hong Kong and China presented a protocol for generating human iPSCs from exfoliated renal epithelial cells present in urine on Nature Protocols.[16] This method of acquiring donor cells is comparatively less invasive and simple. The team reported the induction procedure to take less time, around 2 weeks for the urinary cell culture and 3 to 4 weeks for the reprogramming; and higher yield, up to 4% using retroviral delivery of exogenous factors. Urinary iPSCs (UiPSCs) were found to show good differentiation potential, and thus represent an alternative choice for producing pluripotent cells from normal individuals or patients with genetic diseases, including those affecting the kidney.[16]

Although the methods pioneered by Yamanaka and others have demonstrated that adult cells can be reprogrammed to iPS cells, there are still challenges associated with this technology:

The table at right summarizes the key strategies and techniques used to develop iPS cells over the past half-decade. Rows of similar colors represents studies that used similar strategies for reprogramming.

One of the main strategies for avoiding problems (1) and (2) has been to use small compounds that can mimic the effects of transcription factors. These molecule compounds can compensate for a reprogramming factor that does not effectively target the genome or fails at reprogramming for another reason; thus they raise reprogramming efficiency. They also avoid the problem of genomic integration, which in some cases contributes to tumor genesis. Key studies using such strategy were conducted in 2008. Melton et al. studied the effects of histone deacetylase (HDAC) inhibitor valproic acid. They found that it increased reprogramming efficiency 100-fold (compared to Yamanakas traditional transcription factor method).[25] The researchers proposed that this compound was mimicking the signaling that is usually caused by the transcription factor c-Myc. A similar type of compensation mechanism was proposed to mimic the effects of Sox2. In 2008, Ding et al. used the inhibition of histone methyl transferase (HMT) with BIX-01294 in combination with the activation of calcium channels in the plasma membrane in order to increase reprogramming efficiency.[26] Deng et al. of Beijing University reported on July 2013 that induced pluripotent stem cells can be created without any genetic modification. They used a cocktail of seven small-molecule compounds including DZNep to induce the mouse somatic cells into stem cells which they called CiPS cells with the efficiency at 0.2% comparable to those using standard iPSC production techniques. The CiPS cells were introduced into developing mouse embryos and were found to contribute to all major cells types, proving its pluripotency.[27][28]

Ding et al. demonstrated an alternative to transcription factor reprogramming through the use of drug-like chemicals. By studying the MET (mesenchymal-epithelial transition) process in which fibroblasts are pushed to a stem-cell like state, Dings group identified two chemicals ALK5 inhibitor SB431412 and MEK (mitogen-activated protein kinase) inhibitor PD0325901 which was found to increase the efficiency of the classical genetic method by 100 fold. Adding a third compound known to be involved in the cell survival pathway, Thiazovivin further increases the efficiency by 200 fold. Using the combination of these three compounds also decreased the reprogramming process of the human fibroblasts from four weeks to two weeks. [29][30]

Another key strategy for avoiding problems such as tumor genesis and low throughput has been to use alternate forms of vectors: adenovirus, plasmids, and naked DNA and/or protein compounds.

In 2008, Hochedlinger et al. used an adenovirus to transport the requisite four transcription factors into the DNA of skin and liver cells of mice, resulting in cells identical to ESCs. The adenovirus is unique from other vectors like viruses and retroviruses because it does not incorporate any of its own genes into the targeted host and avoids the potential for insertional mutagenesis.[31] In 2009, Freed et al. demonstrated successful reprogramming of human fibroblasts to iPS cells.[32] Another advantage of using adenoviruses is that they only need to present for a brief amount of time in order for effective reprogramming to take place.

Also in 2008, Yamanaka et al. found that they could transfer the four necessary genes with a plasmid.[33] The Yamanaka group successfully reprogrammed mouse cells by transfection with two plasmid constructs carrying the reprogramming factors; the first plasmid expressed c-Myc, while the second expressed the other three factors (Oct4, Klf4, and Sox2). Although the plasmid methods avoid viruses, they still require cancer-promoting genes to accomplish reprogramming. The other main issue with these methods is that they tend to be much less efficient compared to retroviral methods. Furthermore, transfected plasmids have been shown to integrate into the host genome and therefore they still pose the risk of insertional mutagenesis. Because non-retroviral approaches have demonstrated such low efficiency levels, researchers have attempted to effectively rescue the technique with what is known as the piggyBac transposon system. The lifecycle of this system is shown below. Several studies have demonstrated that this system can effectively deliver the key reprogramming factors without leaving any footprint mutations in the host cell genome. As demonstrated in the figure, the piggyBac transposon system involves the re-excision of exogenous genes, which eliminates issues like insertional mutagenesis

In January 2014, two articles were published claiming that a type of pluripotent stem cell can be generated by subjecting the cells to certain types of stress (bacterial toxin, a low pH of 5.7, or physical squeezing); the resulting cells were called STAP cells, for stimulus-triggered acquisition of pluripotency.[34]

In light of difficulties that other labs had replicating the results of the surprising study, in March 2014, one of the co-authors has called for the articles to be retracted.[35] On 4 June 2014, the lead author, Obokata agreed to retract both the papers [36] after she was found to have committed research misconduct as concluded in an investigation by RIKEN on 1 April 2014.[37]

Studies by Blelloch et al. in 2009 demonstrated that expression of ES cell-specific microRNA molecules (such as miR-291, miR-294 and miR-295) enhances the efficiency of induced pluripotency by acting downstream of c-Myc .[38] More recently (in April 2011), Morrisey et al. demonstrated another method using microRNA that improved the efficiency of reprogramming to a rate similar to that demonstrated by Ding. MicroRNAs are short RNA molecules that bind to complementary sequences on messenger RNA and block expression of a gene. Morriseys team worked on microRNAs in lung development, and hypothesized that their microRNAs perhaps blocked expression of repressors of Yamanakas four transcription factors. Possible mechanisms by which microRNAs can induce reprogramming even in the absence of added exogenous transcription factors, and how variations in microRNA expression of iPS cells can predict their differentiation potential discussed by Xichen Bao et al.[39]

[citation needed]

The generation of iPS cells is crucially dependent on the genes used for the induction.

Oct-3/4 and certain members of the Sox gene family (Sox1, Sox2, Sox3, and Sox15) have been identified as crucial transcriptional regulators involved in the induction process whose absence makes induction impossible. Additional genes, however, including certain members of the Klf family (Klf1, Klf2, Klf4, and Klf5), the Myc family (c-myc, L-myc, and N-myc), Nanog, and LIN28, have been identified to increase the induction efficiency.

Induced pluripotent stem cells are similar to natural pluripotent stem cells, such as embryonic stem (ES) cells, in many aspects, such as the expression of certain stem cell genes and proteins, chromatin methylation patterns, doubling time, embryoid body formation, teratoma formation, viable chimera formation, and potency and differentiability, but the full extent of their relation to natural pluripotent stem cells is still being assessed.[42]

Gene expression and genome-wide H3K4me3 and H3K27me3 were found to be extremely similar between ES and iPS cells.[43][citation needed] The generated iPSCs were remarkably similar to naturally isolated pluripotent stem cells (such as mouse and human embryonic stem cells, mESCs and hESCs, respectively) in the following respects, thus confirming the identity, authenticity, and pluripotency of iPSCs to naturally isolated pluripotent stem cells:

Recent achievements and future tasks for safe iPSC-based cell therapy are collected in the review of Okano et al.[54]

The task of producing iPS cells continues to be challenging due to the six problems mentioned above. A key tradeoff to overcome is that between efficiency and genomic integration. Most methods that do not rely on the integration of transgenes are inefficient, while those that do rely on the integration of transgenes face the problems of incomplete reprogramming and tumor genesis, although a vast number of techniques and methods have been attempted. Another large set of strategies is to perform a proteomic characterization of iPS cells. The Wu group at Stanford University has made significant progress with this strategy.[55] Further studies and new strategies should generate optimal solutions to the five main challenges. One approach might attempt to combine the positive attributes of these strategies into an ultimately effective technique for reprogramming cells to iPS cells.

Another approach is the use of iPS cells derived from patients to identify therapeutic drugs able to rescue a phenotype. For instance, iPS cell lines derived from patients affected by ectodermal dysplasia syndrome (EEC), in which the p63 gene is mutated, display abnormal epithelial commitment that could be partially rescued by a small compound[56]

An attractive feature of human iPS cells is the ability to derive them from adult patients to study the cellular basis of human disease. Since iPS cells are self-renewing and pluripotent, they represent a theoretically unlimited source of patient-derived cells which can be turned into any type of cell in the body. This is particularly important because many other types of human cells derived from patients tend to stop growing after a few passages in laboratory culture. iPS cells have been generated for a wide variety of human genetic diseases, including common disorders such as Down syndrome and polycystic kidney disease.[57][58] In many instances, the patient-derived iPS cells exhibit cellular defects not observed in iPS cells from healthy patients, providing insight into the pathophysiology of the disease.[59] An international collaborated project, StemBANCC, was formed in 2012 to build a collection of iPS cell lines for drug screening for a variety of disease. Managed by the University of Oxford, the effort pooled funds and resources from 10 pharmaceutical companies and 23 universities. The goal is to generate a library of 1,500 iPS cell lines which will be used in early drug testing by providing a simulated human disease environment.[60]

A proof-of-concept of using induced pluripotent stem cells (iPSCs) to generate human organ for transplantation was reported by researchers from Japan. Human liver buds (iPSC-LBs) were grown from a mixture of three different kinds of stem cells: hepatocytes (for liver function) coaxed from iPSCs; endothelial stem cells (to form lining of blood vessels) from umbilical cord blood; and mesenchymal stem cells (to form connective tissue). This new approach allows different cell types to self-organize into a complex organ, mimicking the process in fetal development. After growing in vitro for a few days, the liver buds were transplanted into mice where the liver quickly connected with the host blood vessels and continued to grow. Most importantly, it performed regular liver functions including metabolizing drugs and producing liver-specific proteins. Further studies will monitor the longevity of the transplanted organ in the host body (ability to integrate or avoid rejection) and whether it will transform into tumors.[61][62] Using this method, cells from one mouse could be used to test 1,000 drug compounds to treat liver disease, and reduce animal use by up to 50,000.[63]

Embryonic cord-blood cells were induced into pluripotent stem cells using plasmid DNA. Using cell surface endothelial/pericytic markers CD31 and CD146, researchers identified 'vascular progenitor', the high-quality, multipotent vascular stem cells. After the iPS cells were injected directly into the vitreous of the damaged retina of mice, the stem cells engrafted into the retina, grew and repaired the vascular vessels.[64][65]

In a study conducted in China in 2013, Superparamagnetic iron oxide (SPIO) particles were used to label iPSCs-derived NSCs in vitro. Labeled NSCs were implanted into TBI rats and SCI monkeys 1 week after injury, and then imaged using gradient reflection echo (GRE) sequence by 3.0T magnetic resonance imaging (MRI) scanner. MRI analysis was performed at 1, 7, 14, 21, and 30 days, respectively, following cell transplantation. Pronounced hypointense signals were initially detected at the cell injection sites in rats and monkeys and were later found to extend progressively to the lesion regions, demonstrating that iPSCs-derived NSCs could migrate to the lesion area from the primary sites. The therapeutic efficacy of iPSCs-derived NSCs was examined concomitantly through functional recovery tests of the animals. In this study, we tracked iPSCs-derived NSCs migration in the CNS of TBI rats and SCI monkeys in vivo for the first time. Functional recovery tests showed obvious motor function improvement in transplanted animals. These data provide the necessary foundation for future clinical application of iPSCs for CNS injury.[66]

In 2014, type O red blood cells were synthesized at the Scottish National Blood Transfusion Service from iPSC. The cells were induced to become a mesoderm and then blood cells and then red blood cells. The final step was to make them eject their nuclei and mature properly. Type O can be transfused into all patients. Each pint of blood contains about two trillion red blood cells, while some 107 million blood donations are collected globally every year. Human transfusions were not expected to begin until 2016.[67]

The first human clinical trial using autologous iPSCs is approved by the Japan Ministry Health and will be conducted in 2014 in Kobe. iPSCs derived from skin cells from six patients suffering from wet age-related macular degeneration will be reprogrammed to differentiate into retinal pigment epithelial (RPE) cells. The cell sheet will be transplanted into the affected retina where the degenerated RPE tissue has been excised. Safety and vision restoration monitoring is expected to last one to three years.[68][69] The benefits of using autologous iPSCs are that there is theoretically no risk of rejection and it eliminates the need to use embryonic stem cells.[69]

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What are Stem Cells? Medical News Today

Saturday, August 15th, 2015

knowledge center home stem cell research all about stem cells what are stem cells?

Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources:

Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as skin, muscle, bone, etc.).

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.

Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.

Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several eggs are fertilized in a test tube, but only one is implanted into a woman.

Sexual reproduction begins when a male's sperm fertilizes a female's ovum (egg) to form a single cell called a zygote. The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days - before implantation in the uterus - this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass (embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is the source of embryonic stem cells - totipotent cells (cells with total potential to develop into any cell in the body).

In a normal pregnancy, the blastocyst stage continues until implantation of the embryo in the uterus, at which point the embryo is referred to as a fetus. This usually occurs by the end of the 10th week of gestation after all major organs of the body have been created.

However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the "inner cell mass" of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.

Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted, scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.

Once stem cells have been allowed to divide and propagate in a controlled culture, the collection of healthy, dividing, and undifferentiated cells is called a stem cell line. These stem cell lines are subsequently managed and shared among researchers. Once under control, the stem cells can be stimulated to specialize as directed by a researcher - a process known as directed differentiation. Embryonic stem cells are able to differentiate into more cell types than adult stem cells.

Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are the most potent since they must become every type of cell in the body. The full classification includes:

Embryonic stem cells are considered pluripotent instead of totipotent because they do not have the ability to become part of the extra-embryonic membranes or the placenta.

A video on how stem cells work and develop.

Although there is not complete agreement among scientists of how to identify stem cells, most tests are based on making sure that stem cells are undifferentiated and capable of self-renewal. Tests are often conducted in the laboratory to check for these properties.

One way to identify stem cells in a lab, and the standard procedure for testing bone marrow or hematopoietic stem cell (HSC), is by transplanting one cell to save an individual without HSCs. If the stem cell produces new blood and immune cells, it demonstrates its potency.

Clonogenic assays (a laboratory procedure) can also be employed in vitro to test whether single cells can differentiate and self-renew. Researchers may also inspect cells under a microscope to see if they are healthy and undifferentiated or they may examine chromosomes.

To test whether human embryonic stem cells are pluripotent, scientists allow the cells to differentiate spontaneously in cell culture, manipulate the cells so they will differentiate to form specific cell types, or inject the cells into an immunosuppressed mouse to test for the formation of a teratoma (a benign tumor containing a mixture of differentiated cells).

Scientists and researchers are interested in stem cells for several reasons. Although stem cells do not serve any one function, many have the capacity to serve any function after they are instructed to specialize. Every cell in the body, for example, is derived from first few stem cells formed in the early stages of embryological development. Therefore, stem cells extracted from embryos can be induced to become any desired cell type. This property makes stem cells powerful enough to regenerate damaged tissue under the right conditions.

Tissue regeneration is probably the most important possible application of stem cell research. Currently, organs must be donated and transplanted, but the demand for organs far exceeds supply. Stem cells could potentially be used to grow a particular type of tissue or organ if directed to differentiate in a certain way. Stem cells that lie just beneath the skin, for example, have been used to engineer new skin tissue that can be grafted on to burn victims.

A team of researchers from Massachusetts General Hospital reported in PNAS Early Edition (July 2013 issue) that they were able to create blood vessels in laboratory mice using human stem cells.

The scientists extracted vascular precursor cells derived from human-induced pluripotent stem cells from one group of adults with type 1 diabetes as well as from another group of healthy adults. They were then implanted onto the surface of the brains of the mice.

Within two weeks of implanting the stem cells, networks of blood-perfused vessels had been formed - they lasted for 280 days. These new blood vessels were as good as the adjacent natural ones.

The authors explained that using stem cells to repair or regenerate blood vessels could eventually help treat human patients with cardiovascular and vascular diseases.

Additionally, replacement cells and tissues may be used to treat brain disease such as Parkinson's and Alzheimer's by replenishing damaged tissue, bringing back the specialized brain cells that keep unneeded muscles from moving. Embryonic stem cells have recently been directed to differentiate into these types of cells, and so treatments are promising.

Healthy heart cells developed in a laboratory may one day be transplanted into patients with heart disease, repopulating the heart with healthy tissue. Similarly, people with type I diabetes may receive pancreatic cells to replace the insulin-producing cells that have been lost or destroyed by the patient's own immune system. The only current therapy is a pancreatic transplant, and it is unlikely to occur due to a small supply of pancreases available for transplant.

Adult hematopoietic stem cells found in blood and bone marrow have been used for years to treat diseases such as leukemia, sickle cell anemia, and other immunodeficiencies. These cells are capable of producing all blood cell types, such as red blood cells that carry oxygen to white blood cells that fight disease. Difficulties arise in the extraction of these cells through the use of invasive bone marrow transplants. However hematopoietic stem cells have also been found in the umbilical cord and placenta. This has led some scientists to call for an umbilical cord blood bank to make these powerful cells more easily obtainable and to decrease the chances of a body's rejecting therapy.

Another reason why stem cell research is being pursued is to develop new drugs. Scientists could measure a drug's effect on healthy, normal tissue by testing the drug on tissue grown from stem cells rather than testing the drug on human volunteers.

The debates surrounding stem cell research primarily are driven by methods concerning embryonic stem cell research. It was only in 1998 that researchers from the University of Wisconsin-Madison extracted the first human embryonic stem cells that were able to be kept alive in the laboratory. The main critique of this research is that it required the destruction of a human blastocyst. That is, a fertilized egg was not given the chance to develop into a fully-developed human.

The core of this debate - similar to debates about abortion, for example - centers on the question, "When does life begin?" Many assert that life begins at conception, when the egg is fertilized. It is often argued that the embryo deserves the same status as any other full grown human. Therefore, destroying it (removing the blastocyst to extract stem cells) is akin to murder. Others, in contrast, have identified different points in gestational development that mark the beginning of life - after the development of certain organs or after a certain time period.

People also take issue with the creation of chimeras. A chimera is an organism that has both human and animal cells or tissues. Often in stem cell research, human cells are inserted into animals (like mice or rats) and allowed to develop. This creates the opportunity for researchers to see what happens when stem cells are implanted. Many people, however, object to the creation of an organism that is "part human".

The stem cell debate has risen to the highest level of courts in several countries. Production of embryonic stem cell lines is illegal in Austria, Denmark, France, Germany, and Ireland, but permitted in Finland, Greece, the Netherlands, Sweden, and the UK. In the United States, it is not illegal to work with or create embryonic stem cell lines. However, the debate in the US is about funding, and it is in fact illegal for federal funds to be used to research stem cell lines that were created after August 2001.

Medical News Today is a leading resource for the latest headlines on stem cell research. So, check out our stem cell research news section. You can also sign up to our weekly or daily newsletters to ensure that you stay up-to-date with the latest news.

This stem cells information section was written by Peter Crosta for Medical News Today in September 2008 and was last updated on 19 July 2013. The contents may not be re-produced in any way without the permission of Medical News Today.

Disclaimer: This informational section on Medical News Today is regularly reviewed and updated, and provided for general information purposes only. The materials contained within this guide do not constitute medical or pharmaceutical advice, which should be sought from qualified medical and pharmaceutical advisers.

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