StemCell Therapy

ScienceDaily (Oct. 2, 2012) The team led by Manel Esteller, director of the Cancer Epigenetics and Biology Program in the Bellvitge Biomedical Research Institute (IDIBELL), Professor of Genetics at the University of Barcelona and ICREA researcher, has identified epigenetic changes that occur in adult stem cells to generate different body tissues.

The finding is published this week in The American Journal of Pathology.

The genome of every single cell in the human body is the same, regardless of their appearance and function. Therefore the activity of the tissues and organs and its disorders in complex diseases, such as cancer, cannot be fully explained by the genome. It is necessary something more, and part of the explanation is provided by epigenetics, which is defined as "the inheritance of DNA activity that does not depend on strict sequence of it." That is, if genetics is the alphabet, spelling would be the epigenetics, which refers to chemical changes in our genetic material and their regulatory proteins. The most known epigenetic mark is the addition of a methyl group to DNA. Thus, the epigenome is getting all the epigenetic marks of a living being.

Adult stem cells have an enormous potential to regenerate damaged organs and their use also avoids ethical complications involving embryonic stem cells, as well as technical problems arising from induced stem cells. In this study, researchers have isolated stem cells from body fat and transformed them into muscle and bone cells. Then, it was necessary to know how much resembled are the cells created in the laboratory with those present in one individual and if they were biologically secured enough to be implanted in patients. The study shows that the epigenome of the cells obtained in culture closely resembles that of skeletal muscle cells and they are spontaneously present in nature, although not completely identical.

A key point of the study is that muscle and bone cells produced in the laboratory do not have the tumour epigenome derived from these tumour tissues (rhabdomyosarcoma and osteosarcoma, respectively) so they are safe from a biological perspective. The study coordinator, Manel Esteller, stresses that the research "demonstrates the usefulness of epigenetics in determining the degree of maturity and biosecurity of differentiated tissues used in regenerative medicine against different diseases."

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The above story is reprinted from materials provided by IDIBELL-Bellvitge Biomedical Research Institute.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Adult stem cells change their epigenome to generate new organs

For more than 40 years, Lesley Kelly of Glasgow, Scotland, lived with third-degree burns that stretched over 60 percent of her body.

Kelly was 2 years old when she fell into a bathtub filled with hot water that scorched most of the right side of her body. She lost full range of motion around many of her joints.

"When you have bad scarring, the buildup is very thick and has no elasticity," said Kelly, 45, whose right elbow was most affected by the buildup of scar tissue. "The problem with thermal burn scarring [is that] it's hard to get the range of motion."

Kelly underwent numerous reparative surgeries through the years, but the scar tissue continued to grow back. The procedures did not lessen the look of her scars.

In 2011, Kelly underwent a new, experimental procedure that used stem cells from her own fat tissue to repair the buildup around her right elbow.

Surgeons cleaned the scar buildup around the elbow and used liposuction to pull fat from off Kelly's waist. They separated the fat cells from the stem and regenerative cells, which were then injected into the wound on Kelly's arm. The procedure took less than two hours.

Within months, Kelly was able to regain 40 degrees of motion that she had lost more than 40 years ago.

Cytori Therapeutics, Inc.

"If this technology was available earlier in my life, my scars would not have been as bad," said Kelly.

There are an estimated 50,000 to 70,000 burn cases each year in the U.S., according to the American Burn Association.

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Experimental Stem Cell Therapy May Help Burn Victims

Cleveland, OH-- It's almost every woman's dream. Getting rid of unwanted fat and getting a breast enhancement at the same time.

Dr. Lu Jean Feng is one of a handful of surgeons in the country using a revolutionary procedure that separates stem cells found in fat and then redistributing it into the breasts.

Colleen DeVito is a breast cancer survivor and, after a double mastectom,y she wanted a more natural option.

"I had immediate reconstruction using my own muscles, blood vessels and tissue," Colleen says.

She also used a new procedure called Adipocyte Derived Regenerative Stem Cells or ADRCs.

Researchers are studying fat stem cells to potentially treat burns, radiation injuries and inflammatory bowel disease and, while it's been used for the past few years in cosmetic surgery, it's still considered experimental and not FDA approved.

Dr. Feng uses liposuction to remove unwanted fat and then processes the fat in a device that separates the stem cells.

"An enzyme is thrown in there to release all the fat cells and growth factors and immature vessels and stem cells then it's separated from the fat cells and concentrated," Dr. Feng says.

After it's done, what's left is injected and formed into the breast.

"This breast is more of a teardrop shape that follows the natural breast skin lines and this is a great way to fill it and make a more natural looking breast," Dr. Feng says.

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Surgeon Enhances Breast Size With Fat Stem Cells

HOUSTON -

Pandu, the 286-pound Malayan tiger stretched out on the gurney in the Houston Zoo's hospital, had bone chips big ones in his right elbow.

Ivy the leopard, being prepped in another room, also needed medical treatment for her limp. The zoo's 68-pound black cat, which had arthroscopic surgery in 2009, was showing signs of pain again in her elbows.

The zoo staff was worried.

"I imagine we are going to end up euthanizing her at some point if it can't be fixed," said Beth Schaefer, the zoo's curator of carnivores and primates.

With two big cats needing attention, surgeon Brian Beale of Gulf Coast Veterinary Specialists and stem-cell specialists at InGeneron Inc. donated their services to treat the animals. While Beale removed bone chips and cleaned the joints during arthroscopic surgery, InGeneron staffers produced stem cells from each animal's body fat.

When the surgeries were complete, Beale injected the stem cells, which had taken about two hours to process for each big cat, into the animals' joints to promote faster healing.

Pandu, always a big baby looking for attention, was moving a bit slowly the day after surgery.

Feisty Ivy pretended nothing was wrong.

A week after the surgery, Houston Zoo veterinarian Lauren Howard says neither animal has suffered complications. Pandu, with mild swelling, was released into his exhibit half-days on Monday.

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Stem cells help some ailing Houston Zoo creatures

Public release date: 27-Jun-2012 [ | E-mail | Share ]

Contact: Brian Kladko brian.kladko@ubc.ca 604-827-3301 University of British Columbia

University of British Columbia scientists, in collaboration with an industry partner, have successfully reversed diabetes in mice using stem cells, paving the way for a breakthrough treatment for a disease that affects nearly one in four Canadians.

The research by Timothy Kieffer, a professor in the Department of Cellular and Physiological Sciences, and scientists from the New Jersey-based BetaLogics, a division of Janssen Research & Development, LLC, is the first to show that human stem cell transplants can successfully restore insulin production and reverse diabetes in mice. Crucially, they re-created the "feedback loop" that enables insulin levels to automatically rise or fall based on blood glucose levels. The study is published online today in the journal Diabetes.

After the stem cell transplant, the diabetic mice were weaned off insulin, a procedure designed to mimic human clinical conditions. Three to four months later, the mice were able to maintain healthy blood sugar levels even when being fed large quantities of sugar. Transplanted cells removed from the mice after several months had all the markings of normal insulin-producing pancreatic cells.

"We are very excited by these findings, but additional research is needed before this approach can be tested clinically in humans," says Kieffer, a member of UBC's Life Sciences Institute. "The studies were performed in diabetic mice that lacked a properly functioning immune system that would otherwise have rejected the cells. We now need to identify a suitable way of protecting the cells from immune attack so that the transplant can ultimately be performed in the absence of any immunosuppression."

The research was supported by the Canadian Institutes of Health Research, the Stem Cell Network of Canada, Stem Cell Technologies of Vancouver, the JDRF and the Michael Smith Foundation for Health Research.

Diabetes results from insufficient production of insulin by the pancreas. Insulin enables glucose to be stored by the body's muscle, fat and liver and used as fuel; a shortage of insulin leads to high blood sugar that raises the risk of blindness, heart attack, stroke, nerve damage and kidney failure.

Regular injections of insulin are the most common treatment for the type 1 form of this disease, which often strikes young children. Although experimental transplants of healthy pancreatic cells from human donors have shown to be effective, that treatment is severely limited by the availability of donors.

###

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Stem cells can beat back diabetes: UBC research

HOUSTON (AP) - The U.S. Food and Drug Administration has issued a new report criticizing the Texas company that stored adult stem cells from Texas Gov. Rick Perry for use in an experimental procedure for his back pain, according to a newspaper report Monday.

An FDA report obtained by the Houston Chronicle said CellTex Therapeutics cannot guarantee the stem cells it takes from patients remain sterile and alive. The nine-page report dated April 27 says the lab, located in the Houston suburb of Sugar Land, does not have procedures to prevent contamination of products that are supposed to be sterile.

The report also says the lab didnt have written records of investigations into the failure of a batch of cells. It also says the lab has not marked some lab products properly.

The deficiencies identified reflect significant problems, serious issues, said Paul Knoepfler, an associate professor at the University of California-Davis School of Medicine, in an interview with the newspaper. If I were a patient, they would scare me off big time.

CellTex was thrust into the news last year when Perry, then running for the Republican nomination for president, revealed that he had stem cells taken from fat in his body, grown in a lab and then injected into his back during a July operation to address his back pain.

Perrys stem cells were stored and grown at CellTex, the Chronicle reported. The firm is co-owned by Dr. Stanley Jones, Perrys friend who performed the operation.

Subsequently, the Texas Medical Board approved new rules on similar experimental stem cell therapies. Perry appointed the board. The FDA has not approved any adult stem cell therapies for orthopedic use, but experimentation by doctors in the U.S. and abroad is common.

Some scientists tout possible benefits of stem cell treatments, including treatment for heart disease, diabetes and some cancers. Others argue adult stem cell experimentation actually increases the risk of cancer and can cause blood clots.

A Perry spokeswoman called Perrys surgery a success and reaffirmed his commitment to adult stem cell research. She said the FDA report was between the agency and CellTex.

CellTex CEO David Eller said the company invited the FDA inspection, which took place over nearly two weeks in April, according to the report.

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FDA Criticizes Perry’s Stem Cell Lab

HOUSTON -- The U.S. Food and Drug Administration has issued a new report criticizing the Texas company that stored adult stem cells from Texas Gov. Rick Perry for use in an experimental procedure for his back pain, according to a newspaper report Monday.

An FDA report obtained by the Houston Chronicle said CellTex Therapeutics cannot guarantee the stem cells it takes from patients remain sterile and alive. The nine-page report dated April 27 says the lab, located in the Houston suburb of Sugar Land, does not have procedures to prevent contamination of products that are supposed to be sterile.

The report also says the lab didn't have written records of investigations into the failure of a batch of cells. It also says the lab has not marked some lab products properly.

"The deficiencies identified reflect significant problems, serious issues," said Paul Knoepfler, an associate professor at the University of California-Davis School of Medicine, in an interview with the newspaper. "If I were a patient, they would scare me off big time."

CellTex was thrust into the news last year when Perry, then running for the Republican nomination for president, revealed that he had stem cells taken from fat in his body, grown in a lab and then injected into his back during a July operation to address his back pain.

Perry's stem cells were stored and grown at CellTex, the Chronicle reported. The firm is co-owned by Dr. Stanley Jones, Perry's friend who performed the operation.

Subsequently, the Texas Medical Board approved new rules on similar experimental stem cell therapies. Perry appointed the board. The FDA has not approved any adult stem cell therapies for orthopedic use, but experimentation by doctors in the U.S. and abroad is common.

Some scientists tout possible benefits of stem cell treatments, including treatment for heart disease, diabetes and some cancers. Others argue adult stem cell experimentation actually increases the risk of cancer and can cause blood clots.

A Perry spokeswoman called Perry's surgery a "success" and reaffirmed his commitment to adult stem cell research. She said the FDA report was between the agency and CellTex.

CellTex CEO David Eller said the company invited the FDA inspection, which took place over nearly two weeks in April, according to the report.

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FDA: Stem cell lab used by Perry has problems

Mesenchymal Stem Cells (hMSCs) cultured on a Polyacrylamide gel for 7 days: Cells stained in blue are ALP positive which is a marker for osteogenic differentiation, while the cells that contain red oil droplets underwent adipogenic differentiation. Credit: Bojun Li and Prof. Viola Vogel / ETH Zurich

(Phys.org) -- Researchers were positive: a substrates softness influences the behaviour of stem cells in culture. Now other researchers have made a new discovery: the number of anchoring points to which the cells can adhere is pivotal.

How stem cells differentiate is evidently not so much a question of the stiffness of the substrate upon which they thrive, as the cells mechanical anchoring on the substrate surface. This is shown in a study recently published in Nature Materials by researchers from various European universities, including ETH Zurich.

Since 2006 the research community has been convinced that stem cells can feel the softness of materials they grow upon. Scientists mainly drew this conclusion from correlations between the softness of the substrate and the cells behavior.

The new research project, to which ETH-Zurich professor Viola Vogel and her doctoral student Bojun Li made a key contribution, has come to another conclusion. It reveals that the properties of the network structure of polymers are instrumental in regulating the anchoring of the collagen proteins to which the cells ultimately adhere. And these anchors influence the differentiation of stem cells.

Good protein adhesion makes surface seem stiff

In a series of experiments, which Britta Trappmann from Cambridge University partly conducted at ETH Zurich, the cells were applied to two different polymers of the same softness. However, the polymers differed in terms of their surface structure, which regulates the number of firmly anchored collagen proteins.

If the researchers reduced the number of well-anchored proteins on a hard surface, the cells behaved in the same way as on a soft base. If the anchors were close together, the stem cells differentiated into bone cells. If the anchors were further apart, they became fat cells. The simple correlation that a materials stiffness or elasticity can govern the differentiation of stem cells is therefore not universally valid, says Vogel.

Paradigm shift in cultivation of stem cells

With their experiment, the researchers shake a paradigm. In a study conducted in 2006, scientists revealed a connection between polymer stiffness and the degree of cell differentiation. However, the researchers varied the stiffness of the polymer by varying its network structure.

Continued here:
Anchoring points determine fate of stem cells

Drs. Chia Soo andBruno Pault,from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA,have found a way to turn stem cells from fat tissue into bone of higher quality than that grown with prior techniques.

The mesenchymal stem cells (MSCs) isolated from the fat tissue may develop into bone, cartilage, muscle as well as other tissues. More importantly, fat tissue is easily accessible through liposuction.

What is unique about their research is that they were able topurify stem cells from fat tissue relatively quickly. Until now, the isolatedcells were a mixed bag including some not capable of formingbone or it took weeks for researchers to isolate specific stem cells and grow them in a culture, which increased the risk of infection and genetic variability. Adding the growth factor NELL-1 to the mix helped Drs. Soo and Paultaccelerate bone formation in animal models. The hope is that this new technique may replace the need for painful bone grafts and allow patients to quickly grow bones from their own cells.

Source: UCLA Press Release

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Building bones from fat [Life Lines]

Scientists from the University of California have discovered a way to eliminate painful bone grafts by using purified fat stem cells to grow a bone. They claim that adipose, or fat, tissue is thought to be an ideal source of mesenchymal stem cells that can be developed into bone, cartilage, muscle and other tissues. These cells are plentiful and an easily be obtained through procedures like liposuction.

Traditionally, cells taken from fat had to be cultured for weeks to isolate the stem cells which could become bone. This method had lot of risk of developing infection and genetic instability. Another way to grow a bone was through stromal vascular fraction (SVF) method.

Now scientists have used a cell-sorting machine to isolate and purify human perivascular stem cells (hPSC) from adipose tissue and showed that the cells worked far better than traditional methods in creating bone.

"The purified human hPSCs formed significantly more bone in comparison to the SVF by all parameters," said Dr Chia Soo, researcher at the University of California. "And these cells are plentiful enough that patients with not much excess body fat can donate their own fat tissue."

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Scientists' claim that fat stem cells are ideal for developing bone much faster and the bone cultivated from the stem cells are likely to have much better quality than bone grown using traditional methods.

"People have shown that culture-derived cells could grow bone, but ours are a fresh cell population, and we didn't have to go through the culture process, which can take weeks," Soo said. "The best bone graft is still your own bone, but that is in limited supply and sometimes not of good quality. What we show here is a faster and better way to create bone that could have clinical applications."

Scientists believe that in future this method will be used to harness a healthy bone. Doctors would take stem cells from the patient's fat tissue, purify that into hPSCs, and replace the patient's own stem cells with hPSCs and NELL-1 in the area where bone is required.

The hPSCs with NELL-1 could grow into bone inside the patient, eliminating the need for painful bone-graft harvestings. The goal is for the process to isolate the hPSCs and add the NELL-1 with a matrix or scaffold to aid cell adhesion in less than an hour, according to the scientists.

"Excitingly, recent studies have already demonstrated the utility of perivascular stem cells for regeneration of disparate tissue types, including skeletal muscle, lung and even myocardium," said Bruno Pault, a professor of orthopedic surgery at the University of California, Los Angeles.

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Purified Fat Stem Cells Can Grow Bone Faster, Say Scientists

By Daily Mail Reporter

PUBLISHED: 07:22 EST, 11 June 2012 | UPDATED: 07:53 EST, 11 June 2012

Hope: The technique of growing new bones could one day be used to replace serious breaks and treat degenerative illnesses

Scientists have successfully grown living bones in a laboratory using stem cells, in a technique that could in future be used to replace shattered limbs, treat osteoporosis and arthritis and fix defects such as cleft palate.

The researchers took around a month to transform stem cells originally taken from fat tissue into sections of fully-formed bone up to several centimetres long.

Standard bone grafts involve two procedures, to cut bone from elsewhere in the patient's body before transplanting it into the damaged area, which carry the risk of infection and complications. Bone can also be obtained from donations, but this brings the chance of rejection.

The new method would allow bones to be custom made to shape outside the body, using the patients own stem cells, removing the need for a potentially traumatic operation and reducing the likelihood of rejection.

So far the research has been carried out only on animals but a patient trial is planned for later this year.

The Israeli technology, developed by biotech company Bonus BioGroup and researchers at the Technion Institute of Research, involves growing the bone to fit the exact shape and size of the damaged area.

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Scientists grow living bone out of stem cells in bid to treat arthritis, osteoperosis and shattered limbs

Scientists have paved the way for human bones to be replaced with new ones grown outside the body. Photo: iStockphoto

SCIENTISTS have grown human bone from stem cells in a laboratory, paving the way for patients to have broken bones repaired - or even replaced with new ones grown outside the body from their own cells.

Researchers started with stem cells taken from fat tissue. It took about a month to grow them into sections of fully formed living bone up to several centimetres long.

The first trial in patients is on course for later this year, by an Israeli biotechnology company that has been working with academics on the technology.

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Professor Avinoam Kadouri, head of the scientific advisory board for Bonus BioGroup, said: ''We use three-dimensional structures to fabricate the bone in the right shape and geometry. We can grow these bones outside the body and then transplant them to the patient.

''By scanning the damaged bone area, the implant should fit perfectly and merge with the surrounding tissue. There are no rejection problems as the cells come from the patient.''

The technology, developed with researchers at the Technion Institute of Research in Israel, uses three-dimensional scans of damaged bone to build a gel-like scaffold that matches the shape.

Stem cells, known as mesenchymal stem cells, that have the capacity to develop into many other types of body cell, are taken from a patient by liposuction and are then grown into living bone inside a ''bioreactor'' - a machine that provides the conditions to encourage the cells to develop into bone.

Animals have already successfully received bone transplants, but in the latest study, the scientists were able to insert almost 2.5 centimetres of laboratory-grown human bone into a rat's leg bone, where it successfully merged with the remaining animal bone.

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Fixing broken bones a growth industry

"We use three dimensional structures to fabricate the bone in the right shape and geometry. We can grow these bones outside the body and then transplant it to the patient at the right time.

"By scanning the damaged bone area, the implant should fit perfectly and merge with the surrounding tissue. There are no problems with rejection as the cells come from the patient's own body."

The technology, which has been developed along with researchers at the Technion Institute of Research in Israel, uses three dimensional scans of the damaged bone to build a gel-like scaffold that matches the shape.

Stem cells, known as mesenchymal stem cells, which have the capacity to develop into many other types of cell in the body, are obtained from the patient's fat using liposuction.

These are then grown into living bone on the scaffold inside a "bioreactor" an automated machine that provides the right conditions to encourage the cells to develop into bone.

Already animals have successfully received bone transplants. The scientists were able to insert almost an inch of laboratory-grown human bone into the middle section of a rat's leg bone, where it successfully merged with the remaining animal bone.

The technique could ultimately allow doctors to replace bones that have been smashed in accidents, fill in defects where bone is missing such as cleft palate, or carry out reconstructive plastic surgery.

Professor Kadouri said work was also under way to grow the soft cartilage at the ends of bones, which is needed if entire bones are to be produced in a laboratory.

Bone grafts currently involve taking bits of bone from elsewhere in the patients body and transplanting them to the area which is damaged to encourage healing.

More than 250,000 bone grafts are performed in the UK each year, including repairs to damaged jaws and the replacement of bone lost in operations to remove tumours.

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Human bones grown from fat in laboratory

One of the top suspects behind killer vascular diseases is the victim of mistaken identity, according to researchers from the University of California, Berkeley, who used genetic tracing to help hunt down the real culprit.

The guilty party is not the smooth muscle cells within blood vessel walls, which for decades was thought to combine with cholesterol and fat that can clog arteries. Blocked vessels can eventually lead to heart attacks and strokes, which account for one in three deaths in the United States.

Instead, a previously unknown type of stem cell a multipotent vascular stem cell is to blame, and it should now be the focus in the search for new treatments, the scientists report in a new study appearing June 6 in the journal Nature Communications.

"For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease," said principal investigator Song Li, professor of bioengineering and a researcher at the Berkeley Stem Cell Center. "This work should revolutionize therapies for vascular diseases because we now know that stem cells rather than smooth muscle cells are the correct therapeutic target."

The finding that a stem cell population contributes to artery-hardening diseases, such as atherosclerosis, provides a promising new direction for future research, the study authors said.

"This is groundbreaking and provocative work, as it challenges existing dogma," said Dr. Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at UC San Francisco, who provided some of the mouse vascular tissues used by the researchers. "Targeting the vascular stem cells rather than the existing smooth muscle in the vessel wall might be much more effective in treating vascular disease."

It is generally accepted that the buildup of artery-blocking plaque stems from the body's immune response to vessel damage caused by low-density lipoproteins, the bad cholesterol many people try to eliminate from their diets.

Such damage attracts legions of white blood cells and can spur the formation of fibrous scar tissue that accumulates within the vessel, narrowing the blood flow.

The scar tissue, known as neointima, has certain characteristics of smooth muscle, the dominant type of tissue in the blood vessel wall.

Because mature smooth muscle cells no longer multiply and grow, it was theorized that in the course of the inflammatory response, they revert, or de-differentiate, into an earlier state where they can proliferate and form matrices that contribute to plaque buildup.

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HEALTH: The real culprit behind hardened arteries? Stem cells, says landmark study

A newly discovered type of stem cell may be one of the major driving forces behind heart attacks and other killer vascular diseases, according to a new study. The finding may provide a brand new target for future heart disease treatments, the researchers said.

While doctors have long thought that it was the smooth muscle cells within the blood vessel walls that combined with cholesterol and fat to clog the arteries--and developed treatments accordingly--the new research indicates the guilty party may actually be a previously unknown type of stem cell, called a multipotent vascular stem cell.

In a study conducted in mice, researchers found it was these stem cells, rather than muscle cells, that formed the scar tissue that blocks the flow of blood in the arteries and causes them to harden.

According to the researchers, because multipotent stem cells are capable of becoming multiple types of cells, including smooth muscle, nerve, cartilage, bone and fat cells, the ability of the stem cells to form bone or cartilage could explain how a soft artery calcifies and hardens.

We are very confident that vascular stem cells play a much more important role than what was thought previously, principal investigator Dr. Song Li, professor of bioengineering and researcher at the Berkeley Stem Cell Center, told FoxNews.com.

Li said these stem cells appear to be involved in most major vascular diseases such as atherosclerosis and restenosis, or the clogging of the arteries. The researchers also believe the stem cells are involved the repair and diseases of all blood vessels.

The study could potentially lead to an entirely new area of heart disease treatment, as there are no therapies or medications that currently target stem cells.

Previous therapies focused on cholesterol metabolism and killing smooth muscle cells, Li said. This new finding opens a door to new therapies that target the vascular stem cells, not only to block the proliferation of the stem cells but also stop their differentiation into bone, cartilage, and even fat cellsIt will be a new area for vascular biology, medicine and the pharmaceutical industry.

However, Li said it was important to note the stem cells arent all bad they appear to not only be involved with disease development but also in the regeneration of blood vessels after certain surgeries, such as bypass procedures.

The stem cells can do good and bad things, and the fate needs to be controlled after we understand the mechanisms, Li said.

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Stem cells may be to blame for clogged arteries

BERKELEY One of the top suspects behind killer vascular diseases is the victim of mistaken identity, according to researchers from the University of California, Berkeley, who used genetic tracing to help hunt down the real culprit. The guilty party is not the smooth muscle cells within blood vessel walls, which for decades was thought to combine with cholesterol and fat that can clog arteries. Blocked vessels can eventually lead to heart attacks and strokes, which account for one in three deaths in the United States.

Instead, a previously unknown type of stem cell a multipotent vascular stem cell is to blame, and it should now be the focus in the search for new treatments, the scientists report in a new study appearing today (June 6) in the journal Nature Communications.

"For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease," said principal investigator Song Li, professor of bioengineering and a researcher at the Berkeley Stem Cell Center. "This work should revolutionize therapies for vascular diseases because we now know that stem cells rather than smooth muscle cells are the correct therapeutic target."

The finding that a stem cell population contributes to artery-hardening diseases, such as atherosclerosis, provides a promising new direction for future research, the study authors said.

"This is groundbreaking and provocative work, as it challenges existing dogma," said Dr. Deepak Srivastava, who directs cardiovascular and stem cell research at the Gladstone Institutes in San Francisco, and who provided some of the mouse vascular tissues used by the researchers. "Targeting the vascular stem cells rather than the existing smooth muscle in the vessel wall might be much more effective in treating vascular disease."

It is generally accepted that the buildup of artery-blocking plaque stems from the body's immune response to vessel damage caused by low-density lipoproteins, the bad cholesterol many people try to eliminate from their diets. Such damage attracts legions of white blood cells and can spur the formation of fibrous scar tissue that accumulates within the vessel, narrowing the blood flow.

However, no experiments published have directly demonstrated this de-differentiation process, so Li and his research team remained skeptical. They turned to transgenic mice with a gene that caused their mature smooth muscle cells to glow green under a microscope.

In analyzing the cells from cross sections of the blood vessels, they found that more than 90 percent of the cells in the blood vessels were mature smooth muscle cells. They then isolated and cultured the cells taken from the middle layer of the mouse blood vessels.

After one month of cell expansion, the researchers saw a threefold increase in the size of the cell nucleus and the spreading area, along with an increase in stress fibers. Notably, none of the new, proliferating cells glowed green, which meant that their lineage could not be traced back to the mature smooth muscle cells originally isolated from the blood vessels.

"Not only was there a lack of green markers in the cell cultures, but we noticed that another type of cell isolated from the blood vessels exhibited progenitor traits for different types of tissue, not just smooth muscle cells," said Zhenyu Tang, co-lead author of the study and a Ph.D. student in the UC Berkeley-UCSF Graduate Program in Bioengineering.

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Stem cells real culprit behind hardened arteries

ScienceDaily (June 6, 2012) One of the top suspects behind killer vascular diseases is the victim of mistaken identity, according to researchers from the University of California, Berkeley, who used genetic tracing to help hunt down the real culprit.

The guilty party is not the smooth muscle cells within blood vessel walls, which for decades was thought to combine with cholesterol and fat that can clog arteries. Blocked vessels can eventually lead to heart attacks and strokes, which account for one in three deaths in the United States.

Instead, a previously unknown type of stem cell -- a multipotent vascular stem cell -- is to blame, and it should now be the focus in the search for new treatments, the scientists report in a new study appearing June 6 in the journal Nature Communications.

"For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease," said principal investigator Song Li, professor of bioengineering and a researcher at the Berkeley Stem Cell Center. "This work should revolutionize therapies for vascular diseases because we now know that stem cells rather than smooth muscle cells are the correct therapeutic target."

The finding that a stem cell population contributes to artery-hardening diseases, such as atherosclerosis, provides a promising new direction for future research, the study authors said.

"This is groundbreaking and provocative work, as it challenges existing dogma," said Dr. Deepak Srivastava, who directs cardiovascular and stem cell research at the Gladstone Institutes in San Francisco, and who provided some of the mouse vascular tissues used by the researchers. "Targeting the vascular stem cells rather than the existing smooth muscle in the vessel wall might be much more effective in treating vascular disease."

It is generally accepted that the buildup of artery-blocking plaque stems from the body's immune response to vessel damage caused by low-density lipoproteins, the bad cholesterol many people try to eliminate from their diets. Such damage attracts legions of white blood cells and can spur the formation of fibrous scar tissue that accumulates within the vessel, narrowing the blood flow.

The scar tissue, known as neointima, has certain characteristics of smooth muscle, the dominant type of tissue in the blood vessel wall. Because mature smooth muscle cells no longer multiply and grow, it was theorized that in the course of the inflammatory response, they revert, or de-differentiate, into an earlier state where they can proliferate and form matrices that contribute to plaque buildup.

However, no experiments published have directly demonstrated this de-differentiation process, so Li and his research team remained skeptical. They turned to transgenic mice with a gene that caused their mature smooth muscle cells to glow green under a microscope.

In analyzing the cells from cross sections of the blood vessels, they found that more than 90 percent of the cells in the blood vessels were mature smooth muscle cells. They then isolated and cultured the cells taken from the middle layer of the mouse blood vessels.

See the original post:
The real culprit behind hardened arteries? Stem cells, says landmark study

In a finding that could open up a new realm of treatments for cardiovascular disease, UC Berkeley scientists say they've found that hardened arteries are actually caused by rogue stem cells in blood vessels that start multiplying after blood vessel walls are damaged, not by rogue muscle cells as previously suspected.

"For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease," UC Berkeley bioengineering professor Song Li, senior author of a paper documenting the discovery that appeared Wednesday in the journal Nature Communications, said in a statement Wednesday.

The researchers examined cells from mouse blood vessels and found that the ones that proliferated after vascular injury couldn't be traced back to smooth muscle cells, which are commonly thought to be the culprits behind clogged arteries (in combination with cholesterol and fat).

"We did further tests and detected proteins and transcriptional factors that are only found in stem cells. No one knew that these cells existed in the blood vessel walls, because no one looked for them before," co-author Aijun Wang said in a statement.

The team is calling the newly identified stem cell type multipotent vascular stem cells. Their ability to differentiate into a variety of cell types, including bone and cartilage, could explain how blood vessels become hardened and brittle in the later stages of cardiovascular disease, according to Li.

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In further experiments, the scientists confirmed that human blood vessels contain multipotent vascular stem cells after isolating them from arteries and coaxing them to develop into several different cell types.

Artery-blocking plaque forms as part of the body's natural immune response to blood vessel damage caused by low-density lipoprotein,also known as "bad" cholesterol. Researchers used to think that smooth muscle cells along the blood vessel walls helped form plaque by de-differentiating into a stem cell-like state, but Li and his team were suspicious because this process had never been directly documented in experiments.

Li said in an email that the next step is to establish a model for human blood vessel disease that can be used in the lab to screen drug candidates targeting the vascular stem cells.

The team has already applied for a grant from the California Institute for Regenerative Medicine to work on their "blood vessel on a chip," Li says.

Read more here:
Stem Cells Harden Arteries In Mice, Prompting New Theory On The Cause Of Cardiovascular Disease

University of Georgia stem cell researcher Steve Stice shows stem cells from a tank in his lab in Athens, Ga.

WEDNESDAY, June 6 (HealthDay News) -- A previously unknown type of stem cell is the culprit behind blocked blood vessels that can lead to heart attack and stroke, new research in mice suggests.

It's long been believed that smooth muscle cells within blood vessel walls combined with cholesterol and fat to clog arteries. But in research with mice, a team at the University of California, Berkeley found that's not the case.

[Read: Stem Call Study Shows Promising Results Against Heart Failure.]

http://health.usnews.com/health-news/news/articles/2012/05/10/stem-cell-study-shows-promising-results-against-heart-failure

Using genetic tracing, the investigators determined that a type of stem cell called a multipotent vascular stem cell is to blame and said it should be the focus in the search for new treatments.

"For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease," principal investigator Song Li, a professor of bioengineering and a researcher at the Berkeley Stem Cell Center, said in a university news release. "This work should revolutionize therapies for vascular diseases because we now know that stem cells rather than smooth muscle cells are the correct therapeutic target."

The study was published June 6 in the journal Nature Communications.

"This is groundbreaking and provocative work, as it challenges existing dogma," said Dr. Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at UC San Francisco, who provided some of the mouse vascular tissues used in the study.

[Read:Improved Stem Cell Line May Avoid Cancer Risk.]

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Stem Cells Behind Clogged Arteries

June 4, 2012

Some stem cells can trigger tumors, report scientists

Fischbach lab

Stem cells often used in reconstructive surgery following mastectomies and other cancer-removal treatments may pose a danger: Cornell biomedical scientists have discovered that these cells, in contact with even trace amounts of cancer cells, can create a microenvironment suitable for more tumors to grow.

"It is necessary for us not only to think about what happens with these cells in an otherwise healthy patient, but also, what the fate of stem cells may be in a patient who is prone to disease," said Claudia Fischbach-Teschl, assistant professor of biomedical engineering, who led the research published in Proceedings of the National Academy of Sciences, June 4.

The cells the researchers studied are derived from fat and are called adipose-derived stem cells. They are useful for tissue engineering and reconstructive surgery because they are good at taking over healthy tissue function and recruiting new blood vessels to promote healing.

But they might be too good -- that is, the Cornell researchers observed that the presence of cancer cell media -- the soluble material that contains chemicals secreted by tumor cells -- prevents the stem cells from turning into fat cells as would be desired. Instead, they triggered the cells to secrete chemicals known as "factors" that promote blood vessel growth, or angiogenesis, and to develop into myofibroblasts, which are cells known to play a role in tumor development.

These alterations led to a stiffening of the extracellular matrix that surrounds the cells -- the stiffening is a characteristic feature of breast cancer (which is why tumors can be palpated). Myofibroblasts make the surrounding tissue more rigid, and this stiffness triggers more changes in the stem cell behavior that lead to even more tumor-promoting characteristics -- a positive feedback loop.

The researchers observed these changes in in vitro experiments using stem cells and breast cancer cell lines that varied in aggression. First they collected soluble media from tumor cells and observed how the stem cells changed in response. They found that TGF-beta and interleukin-8 are specific tumor-secreted factors that contribute to the stem cells' eventual change in phenotype to myofibroblasts. They confirmed their results with in vivo experiments by injecting stem cells and tumor cells into the mammary glands of mice.

The experimental results are also supported by the fact that obese women are more likely to develop breast cancer. The presence of more adipose tissue means larger numbers of adipose stem cells, and one could hypothesize that the larger stem cell pool could promote tumor-progression processes, Fischbach-Teschl said.

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Some stem cells can trigger tumors, report scientists