StemCell Therapy

UC Irvine scientists studying the role of circadian rhythms in skin stem cells found that this clock plays a key role in coordinating daily metabolic cycles and cell division.

Their research, which appears Jan. 6 in Cell Reports, shows for the first time how the body's intrinsic day-night cycles protect and nurture stem cell differentiation. Furthermore, this work offers novel insights into a mechanism whereby an out of synch circadian clock can contribute to accelerated skin aging and cancers.

Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, focused their efforts on the epidermis, the outermost protective layer of the skin that is maintained and healed by long-lived stem cells.

While the role of the circadian clock in processes such as sleep, feeding behavior and metabolism linked to feeding and fasting are well known, much less is known about whether the circadian clock also regulates stem cell function.

The researchers used novel two-photon excitation and fluorescence lifetime imaging microscopy in Laboratory of Fluorescence Dynamics in UCI's Department of Biomedical Engineering to make sensitive and quantitative measurements of the metabolic state of single cells within the native microenvironment of living tissue.

They discovered that the circadian clock regulates one form of intermediary metabolism in these stem cells, referred to as oxidative phosphorylation. This type of metabolism creates oxygen radicals that can damage DNA and other components of the cell. In fact, one theory of aging posits that aging is caused by the accumulative damage from metabolism-generated oxygen radicals in stem cells.

The Andersen-Gratton study also revealed that the circadian clock within stem cells shifts the timing of cell division such that the stages of the cell division cycle that are most sensitive to DNA damage are avoided during times of maximum oxidative phosphorylation.

Other studies in animals have linked aging to disruption of circadian rhythms, and Andersen said that accelerated aging could be caused by asynchrony in the metabolism and cell proliferation cycles in stem cells.

"Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging," he said.

Andersen adds that it is possible that future studies could advance therapeutic insights from this research.

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Circadian rhythms regulate skin stem cell metabolism and expansion, study finds

Body clock protects cells from metabolism-generated oxygen radical damage during division

Irvine, Calif., Jan. 6, 2015 -- UC Irvine scientists studying the role of circadian rhythms in skin stem cells found that this clock plays a key role in coordinating daily metabolic cycles and cell division.

Their research, which appears Jan. 6 in Cell Reports, shows for the first time how the body's intrinsic day-night cycles protect and nurture stem cell differentiation. Furthermore, this work offers novel insights into a mechanism whereby an out of synch circadian clock can contribute to accelerated skin aging and cancers.

Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, focused their efforts on the epidermis, the outermost protective layer of the skin that is maintained and healed by long-lived stem cells.

While the role of the circadian clock in processes such as sleep, feeding behavior and metabolism linked to feeding and fasting are well known, much less is known about whether the circadian clock also regulates stem cell function.

The researchers used novel two-photon excitation and fluorescence lifetime imaging microscopy in Laboratory of Fluorescence Dynamics in UCI's Department of Biomedical Engineering to make sensitive and quantitative measurements of the metabolic state of single cells within the native microenvironment of living tissue.

They discovered that the circadian clock regulates one form of intermediary metabolism in these stem cells, referred to as oxidative phosphorylation. This type of metabolism creates oxygen radicals that can damage DNA and other components of the cell. In fact, one theory of aging posits that aging is caused by the accumulative damage from metabolism-generated oxygen radicals in stem cells.

The Andersen-Gratton study also revealed that the circadian clock within stem cells shifts the timing of cell division such that the stages of the cell division cycle that are most sensitive to DNA damage are avoided during times of maximum oxidative phosphorylation.

Other studies in animals have linked aging to disruption of circadian rhythms, and Andersen said that accelerated aging could be caused by asynchrony in the metabolism and cell proliferation cycles in stem cells.

"Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging," he said.

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Circadian rhythms regulate skin stem cell metabolism and expansion, UCI study finds

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Newswise In a groundbreaking study that provides scientists with a critical new understanding of stem cell development and its role in disease, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Kathrin Plath, professor of biological chemistry, have established a first-of-its-kind methodology that defines the unique stages by which specialized cells are reprogrammed into stem cells that resemble those found in the embryo.

The study was published online ahead of print in the journal Cell.

Induced pluripotent stem cells (known as iPSCs) are similar to human embryonic stem cells in that both cell types have the unique ability to self-renew and have the flexibility to become any cell in the human body. iPSC cells, however, are generated by reprogramming skin or blood cells and do not require an embryo.

Reprogramming is a long process (about one to two weeks) and largely inefficient, with typically less than one percent of the primary skin or blood cells successfully completing the journey to becoming an iPSC. The exact stages a cell goes through during the reprogramming process are also not well understood. This knowledge is important, as iPSCs hold great promise in the field of regenerative medicine, as they can provide a single source of patient-specific cells to replace those lost to injury or disease. They can also be used to create novel disease models from which new drugs and therapies can be developed.

This research has broad impact, because by deepening our understanding of cell reprogramming we have the potential to improve disease modeling and the generation of better sources of patient-specific specialized cells suitable for replacement therapy, said Plath. This can ultimately benefit patients with new and better treatments for a wide range of diseases.

Drs. Vincent Pasque and Jason Tchieu, postdoctoral fellows in the lab of Dr. Plath and co-first authors of the study, developed a roadmap of the reprogramming process using detailed time-course analyses. They induced the reprogramming of skin cells into iPSC, then observed and analyzed on a daily basis or every other day the process of transformation at the single-cell level. The data were collected and recorded over a period of up to two weeks.

Plaths team found that the changes that happen in cells during reprogramming occur in a sequential stage-by-stage manner, and that importantly, the stages were the same across all the different reprogramming systems and different cell types analyzed.

The exact stage of reprogramming of any cell can now be determined, said Pasque. This study signals a big change in thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner. Most studies to date ignore the stages of reprogramming, but we can now seek to better understand the entire process on both a macro and micro level.

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Scientists Develop Pioneering Method to Define Stages of Stem Cell Reprogramming

In a groundbreaking study that provides scientists with a critical new understanding of stem cell development and its role in disease, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Kathrin Plath, professor of biological chemistry, have established a first-of-its-kind methodology that defines the unique stages by which specialized cells are reprogrammed into stem cells that resemble those found in the embryo.

The study was published online ahead of print in the journal Cell.

Induced pluripotent stem cells (known as iPSCs) are similar to human embryonic stem cells in that both cell types have the unique ability to self-renew and have the flexibility to become any cell in the human body. iPSC cells, however, are generated by reprogramming skin or blood cells and do not require an embryo.

Reprogramming is a long process (about one to two weeks) and largely inefficient, with typically less than one percent of the primary skin or blood cells successfully completing the journey to becoming an iPSC. The exact stages a cell goes through during the reprogramming process are also not well understood. This knowledge is important, as iPSCs hold great promise in the field of regenerative medicine, as they can provide a single source of patient-specific cells to replace those lost to injury or disease. They can also be used to create novel disease models from which new drugs and therapies can be developed.

"This research has broad impact, because by deepening our understanding of cell reprogramming we have the potential to improve disease modeling and the generation of better sources of patient-specific specialized cells suitable for replacement therapy," said Plath. "This can ultimately benefit patients with new and better treatments for a wide range of diseases.

Drs. Vincent Pasque and Jason Tchieu, postdoctoral fellows in the lab of Dr. Plath and co-first authors of the study, developed a roadmap of the reprogramming process using detailed time-course analyses. They induced the reprogramming of skin cells into iPSC, then observed and analyzed on a daily basis or every other day the process of transformation at the single-cell level. The data were collected and recorded over a period of up to two weeks.

Plath's team found that the changes that happen in cells during reprogramming occur in a sequential stage-by-stage manner, and that importantly, the stages were the same across all the different reprogramming systems and different cell types analyzed.

"The exact stage of reprogramming of any cell can now be determined," said Pasque. "This study signals a big change in thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner. Most studies to date ignore the stages of reprogramming, but we can now seek to better understand the entire process on both a macro and micro level."

Plath's team further discovered that the stages of reprogramming to iPSC are different from what was expected. They found that it is not simply the reversed sequence of stages of embryo development. Some steps are reversed in the expected order; others do not actually happen in the exact reverse order and resist a change until late during reprogramming to iPSCs.

"This reflects how cells do not like to change from one specialized cell type to another and resist a change in cell identity," said Pasque. "Resistance to reprogramming also helps to explain why reprogramming takes place only in a very small proportion of the starting cells."

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Pioneering method developed to define stages of stem cell reprogramming

Seal Beach, Laguna Hills, and Lake Forest, California (PRWEB) January 05, 2015

The Irvine Stem Cell Treatment Center announces a series of free public seminars on the use of adult stem cells for various degenerative and inflammatory conditions. They will be provided by Dr. Thomas A. Gionis, Surgeon-in-Chief.

The seminars will be held on Sunday, January 11, 2015, at 2:30pm and 4:30pm at Marie Callenders Grill, 12489 Seal Beach Blvd., Seal Beach, CA 90740; Tuesday, January 13, 2015, at 2:00pm and 4:00pm at Pollys Pies, 23701 Moulton Parkway, Laguna Hills, CA 92653; Friday, January 16, 2015, at 1:30pm and 3:30pm at Marie Callenders Grill, 12489 Seal Beach Blvd., Seal Beach, CA 90740; Saturday, January 17, 2015, at 2:30pm and 4:30pm at Dennys Restaurant, 23515 El Toro Road, Lake Forest, CA 92630. Please RSVP at (949) 679-3889.

The Irvine Stem Cell Treatment Center, along with sister affiliates, the Miami Stem Cell Treatment Center and the Manhattan Regenerative Medicine Medical Group, abide by investigational protocols using adult adipose derived stem cells (ADSCs) which can be deployed to improve patients quality of life for a number of chronic, degenerative and inflammatory conditions and diseases. ADSCs are taken from the patients own adipose (fat) tissue (found within a cellular mixture called stromal vascular fraction (SVF)). ADSCs are exceptionally abundant in adipose tissue. The adipose tissue is obtained from the patient during a 15 minute mini-liposuction performed under local anesthesia in the doctors office. SVF is a protein-rich solution containing mononuclear cell lines (predominantly adult autologous mesenchymal stem cells), macrophage cells, endothelial cells, red blood cells, and important Growth Factors that facilitate the stem cell process and promote their activity.

ADSCs are the body's natural healing cells - they are recruited by chemical signals emitted by damaged tissues to repair and regenerate the bodys injured cells. The Irvine Stem Cell Treatment Center only uses Adult Autologous Stem Cells from a persons own fat No embryonic stem cells are used. Current areas of study include: Emphysema, COPD, Asthma, Heart Failure, Parkinsons Disease, Stroke, Multiple Sclerosis, Lupus, Rheumatoid Arthritis, Crohns Disease, and degenerative orthopedic joint conditions. For more information, or if someone thinks they may be a candidate for one of the adult stem cell protocols offered by the Irvine Stem Cell Treatment Center, they may contact Dr. Gionis directly at (949) 679-3889, or see a complete list of the Centers study areas at: http://www.IrvineStemCellsUSA.com.

About the Irvine Stem Cell Treatment Center: The Irvine Stem Cell Treatment Center, along with sister affiliates, the Miami Stem Cell Treatment Center and the Manhattan Regenerative Medicine Medical Group, is an affiliate of the Cell Surgical Network (CSN); we are located in Irvine and Westlake, California. We provide care for people suffering from diseases that may be alleviated by access to adult stem cell based regenerative treatment. We utilize a fat transfer surgical technology to isolate and implant the patients own stem cells from a small quantity of fat harvested by a mini-liposuction on the same day. The investigational protocols utilized by the Irvine Stem Cell Treatment Center have been reviewed and approved by an IRB (Institutional Review Board) which is registered with the U.S. Department of Health, Office of Human Research Protection; and the study is registered with Clinicaltrials.gov, a service of the U.S. National Institutes of Health (NIH). For more information, visit our websites: http://www.IrvineStemCellsUSA.com, http://www.MiamiStemCellsUSA.com or http://www.NYStemCellsUSA.com.

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The Irvine Stem Cell Treatment Center Announces Adult Stem Cell Public Seminars in Orange County, California

Turning 10 years old may not quite mark adolescence for a human child, but for a major government research effort such as California's stem cell program, it's well past middle age.

So it's a little strange to hear C. Randal Mills, the new president and chief executive of the program known formally as the California Institute for Regenerative Medicine, say it's time to instill in CIRM "a clear sense of mission."

But that's what Mills is planning for the coming year, as he launches CIRM 2.0, a comprehensive reboot of the program.

Mills, a former biotech company chief executive, took over as CIRM's president last May. His first task, he told me, was to "take a step back and look broadly at how we do our business." He reached the conclusion that "there was a lot of room for improvement."

That's a striking admission for a program that already has allocated roughly two-thirds of its original $3-billion endowment.

Biomedical researchers are sure to find a lot to like about CIRM 2.0, especially Mills' commitment to streamline the program's grant and loan approval process for projects aimed at clinical trials of potential therapies. Reviews of applications take about 22 months on average; Mills hopes to cut that to about three months. The process can be made more efficient without sacrificing science: "We need to do it quickly and also focus on quality," he says in a videotaped presentation on the CIRM website. The CIRM board last month approved a six-month, $50-million round of funding under the new system, all to be aimed at testing new therapies.

Yet the focus on drug development shows that CIRM remains a prisoner of the politics that brought it into existence. The Proposition 71 campaign in 2004 employed inflated promises of cures for Parkinson's disease, Alzheimer's, diabetes and other therapy-resistant conditions to goad California voters into approving the $3-billion bond issue ($6 billion with interest) for stem cell research.

CIRM says it has funded clinical trials of 10 therapies and has backed an additional 87 projects "in the later stages of moving toward clinical trials." In scientific terms that's progress, but it may fall short of the public expectations of "cures" stoked by the initiative's promoters 10 years ago.

And that poses a political problem. At its current rate of grant and loan approvals of about $190 million a year, CIRM has enough funding to last until 2020. What happens after that is an open question, but any campaign to seek new public funding may depend on CIRM's having a successful therapy to show off to voters.

Mills says winning approval for more public funding isn't the goal of CIRM 2.0. "It's not our job at CIRM to extend the life of CIRM," he told me. Instead, he couches the need for urgency in terms of serving patients. As chief executive of Maryland-based Osiris Therapeutics, where he worked before joining CIRM, he says, he had "a firsthand view into the significance of stem cell treatment, and of how important urgency is in this game." Osiris received approval from the Food and Drug Administration and Canadian regulators for a stem cell drug to treat children with severe complications from bone marrow and other blood transplants.

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Ten years in, California's stem cell program is getting a reboot

Chuck Bednar for redOrbit.com Your Universe Online

Two-thirds of all adult cancer cases are primarily the result of bad luck, according to the authors of a new study appearing in Fridays edition of the journal Science.

Dr. Bert Vogelstein, the Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, and Dr. Cristian Tomasetti, an assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, developed a statistical model that measured the proportion of cancer incidence across many different tissue types.

They found that two-thirds of adult cancer incidence across tissues occur when the random mutations that take place during stem cell division drive cancer through, while the remaining one-third of cases are the result of environmental factors and inherited genes.

All cancers are caused by a combination of bad luck, the environment and heredity, and weve created a model that may help quantify how much of these three factors contribute to cancer development, explained Dr. Vogelstein, who is also co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their good genes, but the truth is that most of them simply had good luck, he said, adding that that poor lifestyle choices can also contribute to this so-called bad luck factor.

The authors said that the implications of their model could alter the public perception about cancer risk factors, as well as impact the funding of research related to the disease.

If most cancer cases can be explained by random DNA mutations that occur as stem cells divide, explained Dr. Tomasetti, it means that lifestyle changes will be a tremendous help when it comes to preventing some forms of the disease, but will be less effective against other types.

As a result, the medical community should should focus more resources on finding ways to detect such cancers at early, curable stages, he added. He and Vogelstein said that they reached their conclusion by searching scientific literature for data on the cumulative number of total stem cell divisions among 31 tissue types that take place during a persons lifetime.

Stem cells renew themselves, repopulating cells that die off in specific organs, the researchers said. Cancer arises when tissue-specific stem cells experience mutations in which one chemical letter in DNA is erroneously swapped for another during the replication process.

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Two-thirds of cancer cases are "bad luck," study says

Released: 30-Dec-2014 1:50 PM EST Embargo expired: 1-Jan-2015 2:00 PM EST Source Newsroom: Johns Hopkins Medicine Contact Information

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Newswise Scientists from the Johns Hopkins Kimmel Cancer Center have created a statistical model that measures the proportion of cancer incidence, across many tissue types, caused mainly by random mutations that occur when stem cells divide. By their measure, two-thirds of adult cancer incidence across tissues can be explained primarily by bad luck, when these random mutations occur in genes that can drive cancer growth, while the remaining third are due to environmental factors and inherited genes.

All cancers are caused by a combination of bad luck, the environment and heredity, and weve created a model that may help quantify how much of these three factors contribute to cancer development, says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their good genes, but the truth is that most of them simply had good luck, adds Vogelstein, who cautions that poor lifestyles can add to the bad luck factor in the development of cancer.

The implications of their model range from altering public perception about cancer risk factors to the funding of cancer research, they say. If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others, says biomathematician Cristian Tomasetti, Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. We should focus more resources on finding ways to detect such cancers at early, curable stages, he adds.

In a report on the statistical findings, published Jan. 2 in Science, Tomasetti and Vogelstein say they came to their conclusions by searching the scientific literature for information on the cumulative total number of divisions of stem cells among 31 tissue types during an average individuals lifetime. Stem cells self-renew, thus repopulating cells that die off in a specific organ.

It was well-known, Vogelstein notes, that cancer arises when tissue-specific stem cells make random mistakes, or mutations, when one chemical letter in DNA is incorrectly swapped for another during the replication process in cell division. The more these mutations accumulate, the higher the risk that cells will grow unchecked, a hallmark of cancer. The actual contribution of these random mistakes to cancer incidence, in comparison to the contribution of hereditary or environmental factors, was not previously known, says Vogelstein.

To sort out the role of such random mutations in cancer risk, the Johns Hopkins scientists charted the number of stem cell divisions in 31 tissues and compared these rates with the lifetime risks of cancer in the same tissues among Americans. From this so-called data scatterplot, Tomasetti and Vogelstein determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated.

Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue, says Vogelstein. One example, he says, is in colon tissue, which undergoes four times more stem cell divisions than small intestine tissue in humans. Likewise, colon cancer is much more prevalent than small intestinal cancer.

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'Bad Luck' of Random Mutations Plays Predominant Role in Cancer, Study Shows

Abstract: Adipose tissue is an abundant source of mesenchymal stem cells, which have shown promise in the field of regenerative medicine. Furthermore, these cells can be readily harvested in large numbers with low donor-site morbidity. During the past decade, numerous studies have provided preclinical data on the safety and efficacy of adipose-derived stem cells, supporting the use of these cells in future clinical applications. Various clinical trials have shown the regenerative capability of adipose-derived stem cells in subspecialties of medical fields such as plastic surgery, orthopedic surgery, oral and maxillofacial surgery, and cardiac surgery. In addition, a great deal of knowledge concerning the harvesting, characterization, and culture of adipose-derived stem cells has been reported. This review will summarize data from in vitro studies, pre-clinical animal models, and recent clinical trials concerning the use of adipose-derived stem cells in regenerative medicine.

Introduction

In the field of regenerative medicine, basic research and preclinical studies have been conducted to overcome clinical shortcomings with the use of mesenchymal stem cells (MSCs). MSCs are present in adult tissues, including bone marrow and adipose tissue. For many years, bone marrow-derived stem cells (BSCs) were the primary source of stem cells for tissue engineering applications (Caplan, 1991; Pittenger et al., 1999; Caplan, 2007). However, recent studies have shown that subcutaneous adipose tissue provides a clear advantage over other stem cell sources due to the ease with which adipose tissue can be accessed as well as the ease of isolating stem cells from harvested tissue (Schffler et al., 2007). Initial enzymatic digestion of adipose tissue yields a mixture of stromal and vascular cells referred to as the stromal-vascular fraction (SVF) (Traktuev et al., 2008). A putative stem cell population within this SVF was first identified by Zuk et al. and named processed lipoaspirate (PLA) cells (Zuk et al., 2001; Zuk et al., 2002).

There is no consensus when it comes to the nomenclature used to describe progenitor cells from adipose tissue-derived stroma, which can sometimes lead to confusion. The term PLA refers to adipose-derived stromal cells and adipose-derived stem cells (ASCs) and describes cells obtained immediately after collagenase digestion. Accordingly, the term ASC will be used throughout this review.

ASCs exhibit stable growth and proliferation kinetics and can differentiate toward osteogenic, chondrogenic, adipogenic, myogenic, or neurogenic lineages in vitro (Zuk et al., 2002; Izadpanah et al., 2006; Romanov et al., 2005). Furthermore, a group has recently described the isolation and culture of ASCs with multipotent differentiation capacity at the single-cell level (Rodriguez, et al., 2005).

Using these attractive cell populations, recent studies have explored the safety and efficacy of implanted/administrated ASCs in various animal models. Furthermore, clinical trials using ASCs have been initiated in some medical subspecialties. This review summarizes the current preclinical data and ongoing clinical trials and their outcomes in a variety of medical fields.

Characterization and Localization

ASCs express the mesenchymal stem cell markers CD10, CD13, CD29, CD34, CD44, CD54, CD71, CD90, CD105, CD106, CD117, and STRO-1. They are negative for the hematopoietic lineage markers CD45, CD14, CD16, CD56, CD61, CD62E, CD104, and CD106 and for the endothelial cell (EC) markers CD31, CD144, and von Willebrand factor (Zuk et al., 2002; Musina et al., 2005; Romanov et al., 2005). Morphologically, they are fibroblast-like and preserve their shape after expansion in vitro (Zuk et al., 2002; Arrigoni et al., 2009; Zannettino et al., 2008).

The similarities between ASCs and BSCs may indicate that ASCs are derived from circulating BSCs, which infiltrate into the adipose compartment through vessel walls (Zuk et al., 2002; Zannettino et al., 2008; Brighton et al., 1992; Canfield et al., 2000; Bianco et al., 2001). On the other hand, according to a recent theory, these stem cells are actually pericytes (Traktuev et al., 2008; Chen et al., 2009; Crisan et al., 2008; Zannettino et al., 2008; Tintut et al., 2003; Abedin et al., 2004; Amos et al., 2008). Pericytes around microvessels express alpha-smooth muscle actin (-SMA) as well as certain MSC markers (CD44, CD73, CD90, CD105); however, they do not express endothelial or hematopoietic cell markers (Chen et al., 2009). Pericytes adhere, proliferate in culture, sustain their initial antigenic profile, and can differentiate into bone, cartilage and fat cells (Chen et al., 2009). Moreover, injected MSCs migrate to the blood vessels in vivo and become pericytes (Chen et al., 2009). Considering the above-mentioned data, it can be speculated that pericytes are the ancestors of MSCs, but this does not mean that all MSCs are descendants of pericytes (Chen et al., 2009) or that all pericytes are necessarily stem cells (Lin et al., 2008; Traktuev et al., 2008; da Silva et al., 2008; Abedin et al., 2004; Tintut et al., 2003; Zannettino et al., 2008; Amos et al., 2008).

Traktuev et al. (2008) defined a periendothelial pericyte-like subpopulation of ASCs. These cells were CD34+, CD31-, CD45-, and CD144- and expressed mesenchymal cell markers, smooth muscle antigens, and pericytic markers, including chondroitin sulfate proteoglycan (NG2), CD140a, and CD140b (PDGF receptor and , respectively) (Traktuev et al., 2008; Amos et al., 2008). However, Lin et al. (2008) could not co-localize CD34 and CD104b, and thus concluded that CD34+/CD31- cells of adipose vasculature are not pericytes.

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Adipose-derived Stem Cells: Current Findings and Future ...

The body has evolved ways to get rid of faulty stem cells. A University of Colorado Cancer Center study published in the journal Stem Cells shows that one of these ways is a "program" that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever. Radiation makes a stem cell lose its "stemness." That makes sense: you don't want damaged stem cells sticking around to crank out damaged cells.

The study also shows that this same safeguard of "programmed mediocrity" that weeds out stem cells damaged by radiation allows blood cancers to grow in cases when the full body is irradiated. And by reprogramming this safeguard, we may be able to prevent cancer in the aftermath of full body radiation.

"The body didn't evolve to deal with leaking nuclear reactors and CT scans. It evolved to deal with only a few cells at a time receiving dangerous doses of radiation or other insults to their DNA," says James DeGregori, PhD, investigator at the CU Cancer Center, professor of Biochemistry and Molecular Genetics at the CU School of Medicine, and the paper's senior author.

DeGregori, doctoral student Courtney Fleenor, and colleagues explored the effects of full body radiation on the blood stem cells of mice. In this case, radiation increased the probability that cells in the hematopoietic stem cell system would differentiate. Only, while most followed this instruction, a few did not. Stem cells with a very specific mutation were able to disobey the instruction to differentiate and retain their "stemness." Genetic inhibition of the gene C/EBPA allowed a few stem cells to keep the ability to act as stem cells. With competition from other, healthy stem cells removed, the stem cells with reduced C/EBPA were able to dominate the blood cell production system. In this way, the blood system transitioned from C/EBPA+ cells to primarily C/EBPA- cells.

Mutations and other genetic alterations resulting in inhibition of the C/EBPA gene are associated with acute myeloid leukemia in humans. Thus, it's not mutations caused by radiation but a blood system reengineered by faulty stem cells that creates cancer risk in people who have experienced radiation.

"It's about evolution driven by natural selection," DeGregori says. "In a healthy blood system, healthy stem cells out-compete stem cells that happen to have the C/EBPA mutation. But when radiation reduces the heath and robustness (what we call 'fitness') of the stem cell population, the mutated cells that have been there all along are suddenly given the opportunity to take over."

Think about it in terms of chipmunks and squirrels: reducing an ecosystem's population of chipmunks may allow squirrels to flourish -- especially if the way in which chipmunks are reduced changes the ecosystem to favor squirrels, similar to how radiation changes the body in a way that favors C/EBPA-mutant stem cells).

These studies don't just tell us why radiation makes hematopoietic stem cells (HSCs) differentiate; they also show that by activating a stem cell maintenance pathway, we can keep it from happening. Even months after irradiation, artificially activating the NOTCH signaling pathway of irradiated HSCs lets them act "stemmy" again -- restarting the blood cell assembly line in these HSCs that would have otherwise differentiated in response to radiation.

When DeGregori, Fleenor and colleagues activated NOTCH in previously irradiated HSCs, it kept the population of dangerous, C/EBPA cells at bay. Competition from non-C/EBPA-mutant stem cells, with their fitness restored by NOTCH activation, meant that there was no evolutionary space for C/EBPA-mutant stem cells.

"If I were working in a situation in which I was likely to experience full-body radiation, I would freeze a bunch of my HSCs," DeGregori says, explaining that an infusion of healthy HSCs after radiation exposure would likely allow the healthy blood system to out-compete the radiation-exposed HSC with their "programmed mediocrity" (increased differentiation) and even HSC with cancer-causing mutations. "But there's also hope that in the future, we could offer drugs that would restore the fitness of stem cells left over after radiation."

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Reprogramming stem cells may prevent cancer after radiation

The competition for Maryland's stem cell research grants will be stiffer than ever as applications flood in next month, forcing officials to be more selective even as scientists worry that the state's fiscal problems and a new administration in Annapolis may mean smaller budgets in the future.

The Maryland Stem Cell Research Commission received a record 240 letters declaring intent to apply for $10.4 million in grants, officials said this month. While the majority came from researchers, more than a dozen came from startups and other companies and half a dozen for work testing therapies on humans proof that the 8-year-old program is boosting the state's biotechnology industry, officials said.

But that also means the state likely will reject more applications for the grants than in previous years. And with no funding promises from Gov.-elect Larry Hogan and state budget cuts looming, researchers worry there will be less to go around in 2016 and beyond.

The uncertainty comes just as advancements in stem cell science are making more research possible, threatening progress in Maryland even as other states surge forward, researchers said.

"In California, they have $3 billion. Here, we have $10 million a year. It is very hard," said Ricardo Feldman, an associate professor of microbiology and immunology at the University of Maryland School of Medicine. "Not all of us who have exciting results are going to get it, and some of us who do not get funding will not be able to continue what we started, and that will be very sad."

At an annual symposium on state-funded stem cell research this month, state stem cell commission officials said they received letters of intent from a record 16 companies as well as seven proposals for clinical work and 144 proposals for "translational" work research that aims to turn basic science into viable therapies. Applications are due Jan. 15.

Historically, the awards have gone more for university research and projects that are still at least a few steps away from being used in hospitals, but the surge in commercial and clinical work is a product of the state's long-term commitment to the grants, said Dan Gincel, the stem cell research fund's executive director.

The grants help research projects advance to a stage where they can attract backers like drug companies or other for-profit investors, who are more discriminating in the projects they support since many end up going nowhere.

"A long-term commitment is extra important for something so high-risk," Gincel said. "You gain trust that this is going somewhere."

There aren't many investors for researchers to turn to early on, said Jennifer Elisseeff, a professor of biomedical engineering at the Johns Hopkins University who has been part of teams receiving $920,000 in state grants over the past two years. She and colleagues are exploring how to stimulate stem cells to regrow tissues, a project she called "kind of basic science-y but also very applied."

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Record competition for stem cell grants means tough choices for state officials

Dominique Friend doesn't look like she's sick. But the Lansdowne resident often deals with bouts of pain so severe she ends up in the hospital for weeks.

Friend, 44, was born with sickle cell disease, an inherited blood disorder that affects an estimated 90,000 to 100,000 in the U.S., according to Centers for Disease Control and Prevention information.

Her autobiography "Sickle" was released by Tate Publishing on Dec. 9 in a second edition, after she self-published the book in 2009.

In the book, she tells of her struggle with the debilitating disease. Friend said she shared her personal account to raise awareness about the disease, which predominantly affects African-Americans. It is also found in those of Hispanic and Mediterranean descent, according to CDC information.

Friend said for as long as she can recall, she has dealt with painful episodes that are characteristic of sickle cell disease.

Pain develops when sickle-shaped red blood cells, that should be round like a doughnut, block the blood flow to the chest, joints and other parts of the body, Friend explained. It can last for a few hours to a few weeks and such episodes are called "crises," she said.

"I would take the pain of childbirth over a sickle cell crisis any day," said Friend, who has three children, two stepdaughters and two granddaughters.

She has been married to Michael Friend for 18 years.

The painful disease can disrupt learning for children and make it difficult for adults to work, said Dr. Sophie Lanzkron, an assistant professor of medicine and oncology at Johns Hopkins University School of Medicine.

A bone marrow transplant or stem cell transplant is the only cure, according to the CDC website.

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Lansdowne author raises awareness about sickle cell disease

Boston, MA (PRWEB) December 23, 2014

Earlier this year in a June 24 international conference presentation, Dr. James L. Sherley, director of the Adult Stem Cell Technology Center, LLC (ASCTC) focused attention on an often overlooked and under appreciated unique property of adult tissue stem cells. His title Asymmetric Self-Renewal by Distributed Stem Cells: Misunderstood in the Past, Important for the Future, embodied the essence of his message to congress participants. He gave the address at the 4th World Congress on Cell Science and Stem Cell Research in Valencia, Spain.

The international congress was organized by the Omics Group as a part of its mission to foster the dissemination of leading discoveries and advances in life sciences research. Their posting this month of the slides from Dr. Sherley's June 24 keynote address now provides worldwide open access to life sciences investigators - stem cell biologists in particular - of the concepts that he emphasized.

In a 2008 publication [Breast Disease 29, 37-46, 2008], Sherley coined the new term distributed stem cells (DSCs) as a biology-based name for all natural tissue stem cells that are not embryonic in origin. Adult stem cells are included under the DSC heading. DSCs do not make every cell in the body. Their nature is to produce only a limited tissue-specific or organ-specific distribution of the total possible mature cell types. So, for example, liver DSCs make mature liver cells, but not mature cells found in other organs like the lungs.

Since 2001 and the start of "the stem cell debate," Sherley has insisted that only DSCs can be effective for developing new cellular therapies. In his keynote address, he explained to attendees why the counterparts of DSCs human embryonic stem cells (hESCs) and more recently developed induced pluripotent stem cells (iPSCs) could not.

Though many stem cell scientists recognize and acknowledge the genetic defects, incomplete differentiation, and tumor formation problems of hESCs and iPSCs - which their proponents suggest can be solved - few appreciate their greater problem, which cannot be solved. Unlike DSCs, hESCs and iPSCs lack the property of asymmetric self-renewal.

Sherleys main message is that asymmetric self-renewal, which is the gnomonic for DSCs the very property that defines DSCs is essential for effective cellular therapies. Asymmetric self-renewal means that DSCs can actively multiply with simultaneous reproduction of themselves and production of mature cells. This ability allows DSCs to replenish mature cells, which are continuously lost from tissues and organs, but not lose their genetic blueprint required for tissue and organ renewal and repair.

The asymmetric self-renewal of DSCs is a crucial consideration for all aspects of their study and use. Sherley argues that overlooking it is holding back progress in regenerative medicine. Asymmetric self-renewal is the factor that limits the production of DSCs; but it is so unique to them that it can also be used to identify DSCs, which are notorious for being elusive. The ASCTCs patented technologies for producing and counting DSCs for research and clinical development are grounded in the companys special research and bioengineering expertise for DSC asymmetric self-renewal.

Asymmetric self-renewal may even play a role in the efficient production of iPSCs. At the end of his address, Sherley announced the approval of a new ASCTC patent. The patent covers the invention of a method to make iPSCs from DSCs that were produced by regulating their asymmetric self-renewal (U.S. Patent and Trademark Office No. 8,759,098).

The ASCTC anticipates that despite the new technologys origin in DSC research, it will advance human disease research based on iPSCs. Although iPSCs are not suitable for cell therapy applications, they are uniquely able to provide disease research models for hard to obtain cell types found in patients (e.g., brain cells from autism patients, cardiac cells from heart disease patients).

Continued here:
Adult Stem Cell Technology Center, LLCs Director Sherley's Address on Whats Holding Back Regenerative Medicine ...

(New York City) A new test may reveal which patients will respond to treatment for graft versus host disease (GVHD), an often life-threatening complication of stem cell transplants (SCT) used to treat leukemia and other blood disorders, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published online today in the journal Lancet Haematology and in print in the January issue.

Patients with fatal blood cancers like leukemia often require allogenic stem cell SCT to survive. Donor stem cells are transplanted to a recipient, but not without the risk of developing GVHD, a life-threatening complication and major cause of death after SCT. The disease, which can be mild to severe, occurs when the transplanted donor cells (known as the graft) attack the patient (referred to as the host). Symptom severity, however, does not accurately define how patients will respond to treatment and patients are often treated alike with high-dose steroids. Although SCT cures cancer in 50 percent of the patients, 25 percent die from relapsed cancer and there remaining go into remission but later succumb to effects of GVHD.

"High dose steroids is the only proven treatment for GVHD," said James L. M. Ferrara, MD, DSc, Ward-Coleman Chair in Cancer Medicine Professor at the Icahn School of Medicine at Mount Sinai, Director of Hematologic Malignancies Translational Research Center at Tisch Cancer Institute at Mount Sinai. "Those with low-risk GVHD are often over-treated and face significant side-effects from treatment. Patients with high risk GVHD are undertreated and the GVHD progresses, often with fatal consequences. Our goal is to provide the right treatment for each patient. We hope to identify those patients at higher risk and design an aggressive intervention while tailoring a less-aggressive approach for those with low-risk."

Dr. Ferrara, along with a multi-center team of researchers, developed and tested this new scoring system using almost 500 patient blood samples with newly diagnosed GVHD in varying grades from two different centers. They used three validated biomarkers TNFR1, ST2 and Reg3 to create an algorithm that calculated the probability of non-relapse mortality (usually caused by GVHD) that provided three distinct risk scores to predict the patient's response to GVHD treatment.

The acid test was to evaluate the algorithm in a validation set of 300 additional patients from twenty different SCT centers throughout the US. The algorithm worked perfectly, and the cumulative incidence of non-relapse mortality significantly increased as the GVHD score increased, and so the response rate to primary GVHD treatment decreased.

"This new scoring system will help identify patient who may not respond to standard treatments, and may require an experimental and more aggressive approach," said Dr. Ferrara. "And it will also help guide treatment for patients with lower-risk GVHD who may be over-treated. This will allow us to personalize treatment at the onset of the disease. Future algorithms will prove increasingly useful to develop precision medicine for all SCT patients."

In order to capitalize on this discovery, Dr. Ferrara has created the Mount Sinai Acute GVHD International Consortium (MAGIC) which consists of a group of ten SCT centers in the US and Europe who will collaborate to use this new scoring system to test new treatments for acute GVHD. Dr. Ferrara and colleagues have also written a protocol to treat high-risk GVHD that has been approved by the FDA.

###

Co-collaborators included University of Michigan, University of Regensburg, and the Blood and Marrow Clinical Trials Network.

The study was supported by grants from the National Cancer Institute; the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Doris Duke Charitable Fund, the American Cancer Society, and the Judith Devries Fund.

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Test predicts response to treatment for complication of leukemia stem cell treatment

PHILADELPHIA As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei George Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Perhaps most significantly, say the researchers, is the far greater number of fibroblasts available in the body for reprogramming compared to tissue-specific adult stem cells, which makes this new technique well-suited for other cell-based treatments.

The research was supported by the National Institutes of Health (R01-AR054593, P30-AR057217)

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Cutting Out the Cellular Middleman: New Technology Directly Reprograms Skin Fibroblasts For a New Role

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Newswise PHILADELPHIA - As the main component of connective tissue in the body, fibroblasts are the most common type of cell. Taking advantage of that ready availability, scientists from the Perelman School of Medicine at the University of Pennsylvania, the Wistar Institute, Boston University School of Medicine, and New Jersey Institute of Technology have discovered a way to repurpose fibroblasts into functional melanocytes, the body's pigment-producing cells. The technique has immediate and important implications for developing new cell-based treatments for skin diseases such as vitiligo, as well as new screening strategies for melanoma. The work was published this week in Nature Communications.

The new technique cuts out a cellular middleman. Study senior author Xiaowei George Xu, MD, PhD, an associate professor of Pathology and Laboratory Medicine, explains, "Through direct reprogramming, we do not have to go through the pluripotent stem cell stage, but directly convert fibroblasts to melanocytes. So these cells do not have tumorigenicity."

Changing a cell from one type to another is hardly unusual. Nature does it all the time, most notably as cells divide and differentiate themselves into various types as an organism grows from an embryo into a fully-functional being. With stem cell therapies, medicine is learning how to tap into such cell specialization for new clinical treatments. But controlling and directing the process is challenging. It is difficult to identify the specific transcription factors needed to create a desired cell type. Also, the necessary process of first changing a cell into an induced pluripotent stem cell (iPSC) capable of differentiation, and then into the desired type, can inadvertently create tumors.

Xu and his colleagues began by conducting an extensive literature search to identify 10 specific cell transcription factors important for melanocyte development. They then performed a transcription factor screening assay and found three transcription factors out of those 10 that are required for melanocytes: SOX10, MITF, and PAX3, a combination dubbed SMP3.

"We did a huge amount of work," says Xu. "We eliminated all the combinations of the other transcription factors and found that these three are essential."

The researchers first tested the SMP3 combination in mouse embryonic fibroblasts, which then quickly displayed melanocytic markers. Their next step used a human-derived SMP3 combination in human fetal dermal cells, and again melanocytes (human-induced melanocytes, or hiMels) rapidly appeared. Further testing confirmed that these hiMels indeed functioned as normal melanocytes, not only in cell culture but also in whole animals, using a hair-patch assay, in which the hiMels generated melanin pigment. The hiMels proved to be functionally identical in every respect to normal melanocytes.

Xu and his colleagues anticipate using their new technique in the treatment of a wide variety of skin diseases, particularly those such as vitiligo for which cell-based therapies are the best and most efficient approach.

The method could also provide a new way to study melanoma. By generating melanocytes from the fibroblasts of melanoma patients, Xu explains, "we can screen not only to find why these patients easily develop melanoma, but possibly use their cells to screen for small compounds that can prevent melanoma from happening."

Read this article:
New Technology Directly Reprograms Skin Fibroblasts For a New Role

Consider the relationship between an air traffic controller and a pilot. The pilot gets the passengers to their destination, but the air traffic controller decides when the plane can take off and when it must wait. The same relationship plays out at the cellular level in animals, including humans. A region of an animal's genome -- the controller -- directs when a particular gene -- the pilot -- can perform its prescribed function.

A new study by cell and systems biologists at the University of Toronto (U of T) investigating stem cells in mice shows, for the first time, an instance of such a relationship between the Sox2 gene which is critical for early development, and a region elsewhere on the genome that effectively regulates its activity. The discovery could mean a significant advance in the emerging field of human regenerative medicine, as the Sox2 gene is essential for maintaining embryonic stem cells that can develop into any cell type of a mature animal.

"We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells," said Professor Jennifer Mitchell of U of T's Department of Cell and Systems Biology, lead invesigator of a study published in the December 15 issue of Genes & Development.

"Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell, a property known as pluripotency. We named the region of the genome that we discovered the Sox2 control region, or SCR," said Mitchell.

Since the sequencing of the human genome was completed in 2003, researchers have been trying to figure out which parts of the genome made some people more likely to develop certain diseases. They have found that the answers are more often in the regions of the human genome that turn genes on and off.

"If we want to understand how genes are turned on and off, we need to know where the sequences that perform this function are located in the genome," said Mitchell. "The parts of the human genome linked to complex diseases such as heart disease, cancer and neurological disorders can often be far away from the genes they regulate, so it can be dificult to figure out which gene is being affected and ultimately causing the disease."

It was previously thought that regions much closer to the Sox2 gene were the ones that turned it on in embryonic stem cells. Mitchell and her colleagues eliminated this possibility when they deleted these nearby regions in the genome of mice and found there was no impact on the gene's ability to be turned on in embryonic stem cells.

"We then focused on the region we've since named the SCR as my work had shown that it can contact the Sox2 gene from its location 100,000 base pairs away," said study lead author Harry Zhou, a former graduate student in Mitchell's lab, now a student at U of T's Faculty of Medicine. "To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells. Once we had a good idea that this region could be acting on the Sox2 gene, we removed the region from the genome and monitored the effect on Sox2."

The researchers discovered that this region is required to both turn Sox2 on, and for the embryonic stem cells to maintain their characteristic appearance and ability to differentiate into all the cell types of the adult organism.

"Just as deletion of the Sox2 gene causes the very early embryo to die, it is likely that an abnormality in the regulatory region would also cause early embryonic death before any of the organs have even formed," said Mitchell. "It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells."

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Cell biologists discover on-off switch for key stem cell gene

TORONTO A Canadian-led international team of researchers has begun solving the mystery of just how a specialized cell taken from a persons skin is reprogrammed into an embryonic-like stem cell, from which virtually any other cell type in the body can be generated.

The research is being touted as a breakthrough in regenerative medicine that will allow scientists to one day harness stem cells to treat or even cure a host of conditions, from blindness and Parkinsons disease to diabetes and spinal cord injuries.

Besides creating the reprogramming roadmap, the scientists also identified a new type of stem cell, called an F-class stem cell due to its fuzzy appearance. Their work is detailed in five papers published Wednesday in the prestigious journals Nature and Nature Communications.

Dr. Andras Nagy, a senior scientist at Mount Sinai Hospital in Toronto, led the team of 50 researchers from Canada, the Netherlands, South Korea and Australia, which spent four years analyzing and cataloguing the day-by-day process that occurs in stem cell reprogramming.

The work builds on the 2006-2007 papers by Shinya Yamanaka, who showed that adult skin cells could be turned into embryonic-like, or pluripotent, stem cells through genetic manipulation, a discovery that garnered the Japanese scientist the Nobel Prize in 2012.

Nagy likened the roughly 21-day process to complete that transformation to a black box, so called because scientists did not know what went on within the cells as they morphed from one cell type into the other.

It was just like a black box, Nagy said Wednesday, following a briefing at the hospital. You start with a skin cell, you arrive at a stem cell but we had no idea what was happening inside the cell.

Nagys team set about cataloguing the changes as they occurred by removing cells from culture dishes at set points during the three-week period, then analyzing such cellular material as DNA and proteins present at that moment.

The result is a database that will be available to scientists around the world, which the team hopes will spur new research to advance the field of stem cell-based regenerative medicine.

Co-author Ian Rogers, a scientist in Nagys lab, said the database will allow researchers to identify various properties of the developing stem cells, which could mean improving their ability to treat or cure disease.

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Canadian-led team of researchers shows how stem cells can be reprogrammed

TORONTO A Canadian-led international team of researchers has begun solving the mystery of just how a specialized cell taken from a persons skin is reprogrammed into an embryonic-like stem cell, from which virtually any other cell type in the body can be generated.

The research is being touted as a breakthrough in regenerative medicine that will allow scientists to one day harness stem cells to treat or even cure a host of conditions, from blindness and Parkinsons disease to diabetes and spinal cord injuries.

Besides creating the reprogramming roadmap, the scientists also identified a new type of stem cell, called an F-class stem cell due to its fuzzy appearance. Their work is detailed in five papers published Wednesday in the prestigious journals Nature and Nature Communications.

Dr. Andras Nagy, a senior scientist at Mount Sinai Hospital in Toronto, led the team of 50 researchers from Canada, the Netherlands, South Korea and Australia, which spent four years analyzing and cataloguing the day-by-day process that occurs in stem cell reprogramming.

The work builds on the 2006-2007 papers by Shinya Yamanaka, who showed that adult skin cells could be turned into embryonic-like, or pluripotent, stem cells through genetic manipulation, a discovery that garnered the Japanese scientist the Nobel Prize in 2012.

Nagy likened the roughly 21-day process to complete that transformation to a black box, so called because scientists did not know what went on within the cells as they morphed from one cell type into the other.

It was just like a black box, Nagy said Wednesday, following a briefing at the hospital. You start with a skin cell, you arrive at a stem cell but we had no idea what was happening inside the cell.

Nagys team set about cataloguing the changes as they occurred by removing cells from culture dishes at set points during the three-week period, then analyzing such cellular material as DNA and proteins present at that moment.

The result is a database that will be available to scientists around the world, which the team hopes will spur new research to advance the field of stem cell-based regenerative medicine.

Co-author Ian Rogers, a scientist in Nagys lab, said the database will allow researchers to identify various properties of the developing stem cells, which could mean improving their ability to treat or cure disease.

Link:
Researchers show how stem cells can be reprogrammed

Professional athletes are getting injections of stem cells to speed up recovery from injury. Critics call it a high-tech placebo.

NFL quarterback Peyton Manning reportedly had a stem cell treatment to his neck in 2011.

Elite athletes do whatever it takes to win. Lately, thats meant getting an injection of their own stem cells.

The treatments, developed over the last eight years, typically involve extracting a small amount of a players fat or bone marrow and then injecting it into an injured joint or a strained tendon to encourage tissue regeneration. Bone marrow contains stem cells capable of generating new blood cells, cartilage, and bone.

Although the treatments have become a multimillion-dollar industry, some doctors say theres only thin medical evidence they actually speed healing. In a report issued last week, public policy researchers at Rice University criticized the National Football Leagues role in promoting unproven treatments to the public. Some players, including Peyton Manning of the Denver Broncos and Sidney Rice, whos now retired but won a Super Bowl with the Seattle Seahawks last year, have reportedly gone overseas for stem cell treatments and others have acted as spokespeople for U.S. clinics offering them.

The Rice researchers, Kirstin Matthews and Maude Cuchiara, say the NFL should create an independent panel and fund research on whether stem cell treatments actually work, similar to what it did after facing questions around concussions and brain injury. I think they should be more proactive. They should get ahead of this one, says Matthews.

Sports Illustrated reports that hundreds of football players have gotten stem cell treatments, with many travelling abroad for types of therapy not offered in the United States.But its not only football players trying them. The tennis player Rafael Nadal is reportedly undergoing stem cell treatments for back pain, and the injections are also being sought out by soccer players and high school athletes.

The NFL didnt respond to questions from MIT Technology Review. Doctors offering the treatments say theyre promising and should be given a chance. Others say theres not enough data. Any of these injections have a placebo effect, says Freddie Fu, an orthopedic surgeon who is chairman of sports medicine at the University of Pittsburgh Medical Center and top doctor for the schools sports teams. We dont know what we are putting in. We dont really know what exactly what it does, biologically.

Orthopedic surgeons hope one day to use stem cells to regenerate cartilage and other lost tissue. But wishful thinking, and profits, have gotten ahead of the facts, says Fu. Theres a lot of marketing in orthopedics right now. I would say 15 to 20 percent of treatments are not effective, he says.

Unlike a drug, which gets tested for years and is then weighed by experts and the U.S. Food and Drug Administration before hitting the market, the bone marrow treatments offered in the U.S. arent regulated.

Link:
The NFL Has a Problem with Stem Cell Treatments