StemCell Therapy

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

SAN DIEGO, CA--(Marketwire -05/30/12)- Cytori Therapeutics (CYTX) has obtained approval to sell the Celution 800 System in Russia for various medical uses. These clinical uses are based on those in the current European CE Mark, and include the use of the Celution system and its output of adipose-derived stem and regenerative cells (ADRCs) for plastic surgery and select soft tissue therapies.

The Celution system and related products will be sold into Russia for these indications exclusively through Cytori's distribution partner Human Stem Cells Institute of Moscow (HSCI). HSCI develops and commercializes a diverse portfolio of cell and gene-based treatments. With Cytori, they intend to initially target physicians and clinics seeking to perform a full range of soft tissue procedures such as injections, autologous fat grafting and tissue repair procedures.

"This regulatory achievement and the distribution partnership with HSCI gives us immediate access to the Russian market through an established and scientifically driven organization with a sales and marketing team already trained and knowledgeable in cell therapy," said Clyde W. Shores, Executive Vice-President of Marketing & Sales. "We anticipate beginning to see the incremental impact from Russian sales starting in the second half of 2012. This approval is an important achievement and helps fulfill our stated 2012 goal to obtain additional market approvals for our technology."

Russia is now the 11th largest medical market in the world and is experiencing double digit growth. The plastic and reconstructive surgery market, which is predominately private pay, represents a part of this growth. Specifically, more than 25,000 anatomical soft tissue augmentations and an additional estimated 12,000 fat grafting procedures are performed each year in Russia.

About Human Stem Cells Institute

Human Stem Cells Institute (eng.hsci.ru) is Russia's first public biotech company and was founded in 2003. The main focus of HSCI is research and development as well as commercialization and marketing of innovative proprietary products and services in the areas of cell-based and gene and post-genomic technologies. Additionally, HSCI owns the largest family cord blood stem cells bank in Russia -- Gemabank.

About Cytori

Cytori Therapeutics, Inc. is developing cell therapies based on autologous adipose-derived regenerative cells (ADRCs) to treat cardiovascular disease and repair soft tissue defects. Our scientific data suggest ADRCs improve blood flow, moderate the immune response and keep tissue at risk of dying alive. As a result, we believe these cells can be applied across multiple "ischemic" conditions. These therapies are made available to the physician and patient at the point-of-care by Cytori's proprietary technologies and products, including the Celution system product family. http://www.cytori.com

Cautionary Statement Regarding Forward-Looking Statements

This communication includes forward-looking statements regarding events, trends and business prospects, which may affect our future operating results and financial position. Such statements, including, but not limited to, those regarding our ability to successfully develop the market for Celution in Russia, are subject to risks and uncertainties that could cause our actual results and financial position to differ materially. Some of these risks and uncertainties include the challenges inherent in convincing physicians and patients to adopt the new technology, creating and implementing a successful marketing and sales strategy, as well as our history of operating losses, regulatory uncertainties, dependence on third party performance, and other risks and uncertainties described under the "Risk Factors" in Cytori's Securities and Exchange Commission Filings, including its annual report on Form 10-K for the year ended December 31, 2011. Cytori assumes no responsibility to update or revise any forward-looking statements contained in this press release to reflect events, trends or circumstances after the date of this press release.

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Cytori Obtains Celution(R) Approval in Russia; To Launch Product Line for Plastic Surgery and Select Soft Tissue ...

ARLINGTON HEIGHTS, Ill., May 29, 2012 (GLOBE NEWSWIRE) -- Adipose stem cells (ACSs)--stem cells derived from fat--are a promising source of cells for use in plastic surgery and regenerative medicine, according to a special review in the June issue of Plastic and Reconstructive Surgery(R), the official medical journal of the American Society of Plastic Surgeons (ASPS).

But much more research is needed to establish the safety and effectiveness of any type of ASC therapy in human patients, according to the article by ASPS Member Surgeon Rod Rohrich, MD of University of Texas Southwestern Medical Center, Dallas, and colleagues. Dr. Rohrich is Editor-in-Chief of Plastic and Reconstructive Surgery.

Adipose Stem Cells--Exciting Possibilities, but Proceed with Caution

The authors present an up-to-date review of research on the science and clinical uses of ASCs. Relatively easily derived from human fat, ASCs are "multipotent" cells that can be induced to develop into other kinds of cells--not only fat cells, but also bone, cartilage and muscle cells.

Adipose stem cells promote the development of new blood vessels (angiogenesis) and seem to represent an "immune privileged" set of cells that blocks inflammation. "Clinicians and patients alike have high expectations that ASCs may well be the answer to curing many recalcitrant diseases or to reconstruct anatomical defects," according to Dr. Rohrich and co-authors.

However, even as the number of studies using ASCs increases, there is continued concern about their "true clinical potential." The reviewers write, "For example, there are questions related to isolation and purification of ASCs, their effect on tumor growth, and the enforcement of FDA regulations."

Dr. Rohrich and co-authors performed an in-depth review to identify all known clinical trials of ASCs. So far, most studies have been performed in Europe and Korea; reflecting stringent FDA regulations, only three ASC studies have been performed in the United States to date.

Many Different Uses, But Little Experience So Far

Most ASC clinical trials to date have been performed in plastic surgery--a field with "unique privileged access to adipose tissues." Plastic surgeon-researchers have used ASCs for several types of soft tissue augmentation, such as breast augmentation (including after implant removal) and regeneration of fat in patients with abnormal fat loss (lipodystrophy). Studies exploring the use of ASCs to promote healing of difficult wounds have been reported as well. They have also been used as a method of soft tissue engineering or tissue regeneration, with inconclusive results.

In other specialties, ASCs have been studied for use in treating certain blood and immunologic disorders, heart and vascular problems, and fistulas. Some studies have explored the use of ASCs for generating new bone for use in reconstructive surgery. A few studies have reported promising preliminary results in the treatment of diabetes, multiple sclerosis, and spinal cord injury. No serious adverse events related to ASCs were reported in either group of studies.

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Fat-Derived Stem Cells Show Promise for Regenerative Medicine, Says Review in Plastic and Reconstructive Surgery(R)

DALLAS, May 29 (UPI) -- Stem cells derived from fat may be a promising source of cells for use in plastic surgery and regenerative medicine, U.S. researchers say.

Dr. Rod Rohrich of the University of Texas Southwestern Medical Center in Dallas said adipose stem cells are "multipotent" cells that can be induced to develop into other kinds of cells -- not only fat cells, but also bone, cartilage and muscle cells.

Adipose stem cells -- relatively easily derived from human fat -- promote the development of new blood vessels and seem to represent an "immune privileged" set of cells that blocks inflammation, Rohrich said.

"Clinicians and patients alike have high expectations that adipose stem cells might well be the answer to curing many recalcitrant diseases or to reconstruct anatomical defects," Rohrich said in a statement.

Rohrich and co-authors conducted an in-depth review to identify all known clinical trials of adipose stem cells, but most studies have been performed in Europe and South Korea. Only three adipose stem cells studies were performed in the United States due to stringent U.S. Food and Drug Administration regulations, Rohrich said.

Although many of the results were encouraging, the reviewers emphasize that all of these applications are in their infancy and worldwide round the world, fewer than 300 patients were treated using adipose stem cells, the study said.

The findings are scheduled to be published in the June issue of Plastic and Reconstructive Surgery.

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Fat-derived stem cells encouraging

By the time Dr. Spencer Misner had carved away the dead and diseased flesh from Bobby Rices right foot last year, little remained other than bones and tendons.

I couldnt believe it. It didnt look real. It looked like something out of a movie, recalled Rice, a Whitfield County resident.

Today, the ankle has almost completely healed. It looks like Rice had simply scraped it. And Rices foot has largely healed, too. Misner credits cutting-edge stem cell treatments for saving Rices foot and leg.

Rice, who has diabetes, stepped on a piece of glass last fall and his foot quickly became infected. After trying a home remedy, Rice eventually went to Daltons Hamilton Medical Center emergency room, where doctors found he had a rapidly spreading necrotizing fasciitis, or in laymans terms, flesh-eating bacteria.

Physicians treated the infection with antibiotics. However, Rice had one toe amputated. Doctors had to strip away much of the flesh from Rices foot and a great deal of flesh along his ankle.

We did what we had to do, Misner said. We got the infection out. We saved his life. But what do you do next? Wed normally say all you can do now is cut of his leg so he can get on with his life.

But Misner had another idea. He contacted Ed Fickey, a sales representative for Osiris Therapeutics and asked about using the companys new stem cell technologies to rebuild the foot and ankle.

Stem cells can grow and differentiate into many different types of cells. Stem cell treatments introduce these cells into damaged or diseased organs to repair them.

The problem is that Bobby is an indigent patient and didnt have the financial resources. Ed spoke to the company, and they agreed to donate the products for free, Misner said.

Osiris provided two products called Grafix and Ovation. Fickey said they are made from adult stem cells derived from donated placenta and do not come from embryos.

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Stem cell treatment regrows Whitfield man’s foot

May 24, 2012

Connie K. Ho for RedOrbit.com

Technology is rapidly progressing and so is research related to stem cells.

Researchers from the University of Michigan recently announced that they found a special surface without biological contaminants that can help adult-derived stem cells to grow and change into different cell types. The findings, published in the journal Stem Cells, are considered a breakthrough in stem cell research.

In the study, scientists grew bone cells on the surface and then transplanted the cells to the skulls of mice to look at the cells regenerative powers. The results showed that the cells produced four times as much new bone growth in mice without the help of extra bone cells. The importance of these adult-derived induced stem cells is that they come from the patient and these cells are compatible for medical treatments.

We turn back the clock, in a way. Were taking a specialized adult cell and genetically reprogramming it, so it behaves like a more primitive cell, commented Paul Krebsbach, professor of biological and materials sciences at the U-M School of Dentistry, on the process of stem cell creation.

In the project, researchers examined how human skin cells are turned into stem cells and, even though they are not exactly sure as to how the process works, how it involves the addition of proteins that can signal the genes to turn on and off to the adult cells. Prior to being used to repair parts of the body, the stem cells are grown and directed to become a specific cell type. Researchers were able to use the surface of the animal cells and proteins for stem cell habitats, but saw that the amount of cells produced could vary by animal.

You dont really know whats in there, noted Joerg Lahann, associate professor of chemical engineering and biomedical engineering.

One difficulty researchers have encountered in the past is the fact that human cells and animals cells can sometimes mix. However, the polymer gel made by Lahann and his fellow researchers helped avoid this problem. Researchers were able to gain better control over the gels ingredients and how they were combined.

Its basically the ease of a plastic dish, Lahann said. There is no biological contamination that could potentially influence your human stem cells.

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Bone Repair Via Stem-cell-growing Surface

ScienceDaily (May 23, 2012) University of Michigan researchers have proven that a special surface, free of biological contaminants, allows adult-derived stem cells to thrive and transform into multiple cell types. Their success brings stem cell therapies another step closer. To prove the cells' regenerative powers, bone cells grown on this surface were then transplanted into holes in the skulls of mice, producing four times as much new bone growth as in the mice without the extra bone cells.

An embryo's cells really can be anything they want to be when they grow up: organs, nerves, skin, bone, any type of human cell. Adult-derived "induced" stem cells can do this and better. Because the source cells can come from the patient, they are perfectly compatible for medical treatments.

In order to make them, Paul Krebsbach, a professor of biological and materials sciences in the School of Dentistry, said, "We turn back the clock, in a way. We're taking a specialized adult cell and genetically reprogramming it, so it behaves like a more primitive cell."

Specifically, they turn human skin cells into stem cells. Less than five years after the discovery of this method, researchers still don't know precisely how it works, but the process involves adding proteins that can turn genes on and off to the adult cells.

Before stem cells can be used to make repairs in the body, they must be grown and directed into becoming the desired cell type. Researchers typically use surfaces of animal cells and proteins for stem cell habitats, but these gels are expensive to make, and batches vary depending on the individual animal.

"You don't really know what's in there," said Joerg Lahann, an associate professor of chemical engineering and biomedical engineering. For example, he said that human cells are often grown over mouse cells, but they can go a little native, beginning to produce some mouse proteins that may invite an attack by a patient's immune system.

The polymer gel created by Lahann and his colleagues in 2010 avoids these problems because researchers are able to control all of the gel's ingredients and how they combine. "It's basically the ease of a plastic dish," said Lahann. "There is no biological contamination that could potentially influence your human stem cells."

Lahann and colleagues had shown that these surfaces could grow embryonic stem cells. Now, Lahann has teamed up with Krebsbach's team to show that the polymer surface can also support the growth of the more medically-promising induced stem cells, keeping them in their high-potential state. To prove that the cells could transform into different types, the team turned them into fat, cartilage, and bone cells.

They then tested whether these cells could help the body to make repairs. Specifically, they attempted to repair 5-millimeter holes in the skulls of mice. The weak immune systems of the mice didn't attack the human bone cells, allowing the cells to help fill in the hole.

After eight weeks, the mice that had received the bone cells had 4.2 times as much new bone, as well as the beginnings of marrow cavities. The team could prove that the extra bone growth came from the added cells because it was human bone.

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Stem-cell-growing surface enables bone repair

Date: Friday May. 25, 2012 9:27 AM ET

CALGARY Calgary scientists say they have revolutionized stem cell production and have found a way to create the super cells without the risk of cancer.

A pair of researchers at the University of Calgary have created a device that allows them to produce millions of cells which can then be reprogrammed to make stem cells.

Dr. Derrick Rancourt and Dr. Roman Krawetz say they have perfected a new bioreactor technology that allows them to make millions of pluripotent stem cells much more quickly than ever before.

Pluripotent stem cells come from two main sources; embryos and adult cells that have been reprogrammed by scientists.

Scientists turn on four specific genes to reprogram the cells into stem cells which results in pluripotent stem cells or iPS cells.

Pluripotent stem cells have the potential to differentiate into almost any cell in the body.

"The even better news is, we made these stem cells without introducing the cancer gene at all," says Rancourt, co-author of the research, published in the May issue of the prestigious journal Nature Methods. "These stem cells are an outstanding alternative to embryonic stem cells."

Up until now, scientists were limited in their research because it usually takes one million adult cells to make a single stem cell and the resulting stem cells are much more likely to cause cancer.

"Scientists can make a whole mouse from iPS cells," says Krawetz. "The challenge they face is, within two years, the mouse gets cancer."

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Calgary scientists make stem cell breakthrough

CALGARY Calgary scientists say they have revolutionized stem cell production and have found a way to create the super cells without the risk of cancer.

Two researchers at the University of Calgary have created a device that allows them to produce millions of cells that can then be reprogrammed to make stem cells.

Dr. Derrick Rancourt and Dr. Roman Krawetz say they have perfected a new bioreactor technology that allows them to make millions of pluripotent stem cells much more quickly than ever before.

Pluripotent stem cells come from two main sources; embryos and adult cells that have been reprogrammed by scientists.

Scientists turn on four specific genes to reprogram the cells into stem cells which results in pluripotent stem cells or iPS cells.

Pluripotent stem cells have the potential to differentiate into almost any cell in the body.

The even better news is, we made these stem cells without introducing the cancer gene at all, says Rancourt, coauthor of the research, published in the May issue of the prestigious journal Nature Methods. These stem cells are an outstanding alternative to embryonic stem cells.

Up until now, scientists were limited in their research because it usually takes one million adult cells to make a single stem cell and the resulting stem cells are much more likely to cause cancer.

Scientists can make a whole mouse from iPS cells, says Krawetz. The challenge they face is, within two years, the mouse gets cancer.

The U of C team has found a way around those limitations.

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Calgary scientists claim they’ve made breakthrough with stem cell production

Fat stem cells may help treat kidney ailments BS Reporter / Mumbai/ AhmedabadMarch 06, 2007 In a breakthrough in the stem cell research, scientist from Ahmedabad have developed a technique to encourage a new kind of stem cells called Mesenchymal stem cells generated from fat (adipose tissue) of donors, which can be used in treating kidney diseases. Mesenchymal stem cells generated from fat of donors hold great promise for the treatment of kidney diseases, claims H L Trivedi, director, Institute of Kidney Diseases and Research Center (IKDRC), Ahmedabad. We will soon patent the research, he added. The institute will soon convene a meeting of scientists working on the project and take a decision on securing the patent for the research. A team of scientists from the IKDRC, led by Trivedi, has clinically proved that when presented in the right physical context, certain growth factors encourage the survival and proliferation of fat mesenchymal stem cells grown outside the body. Trivedi says the research offers hope of cent per cent recovery for patients suffering from severe kidney diseases as the mesenchymal stem cells will nullify the rejection rate of the body, thus inducing the body to accept the newly transplanted kidney as part of its own body. Emphasising on the success of mesenchymal stem cells for kidney treatment, Trivedi further said mesenchymal stem cells were the best repair stem cells compared to other stem cells. The worlds first recipient of these kinds of stem cells is a kidney patient - Hetalben Mewada, a 30-year-old housewife from Palanpur in Gujarat, claims the scientist from IKDRC. Speaking about the financial aspect of the kidney treatment, Trivedi said, Mesenchymal stem cells using fat is simple and cheap. The latest invention would cut the cost of surgery drastically and make it affordable for the needy people. It will also reduce the chances of recurrence and complexity in the post surgery situation, he said. Mesenchymal stem cells are available in bone marrow and peripheral blood cells in smaller quantity, but the cells are not economically feasible. Mesenchymal stem cells can be easily derived from fat and is economically viable. Mesenchymal stem cells that are already in the fats are separated and grown through culturing technique in laboratory. IKDRCs scientists carried out a kidney transplant operation using Mesenchymal stem cells derived from fats along with adult hematopoietic stem cells infused into the transplanted kidney to create tolerance or acceptance by the patients. This eliminates the chance of rejection, and the patients would not need medication. Under this procedure, the mesenchymal stem cells act as a big brother to adult hematopoietic stem cells. Mesenchymal stem cells protect these hematopoietic stem cells and help their grafting into different organs by themselves getting grafted and making space for their younger siblings (adult hematopoietic stem cells) to live along with them in their vicinity. Fat stem cells may help treat kidney ailments BS Reporter / Mumbai/ Ahmedabad Mar 06, 2007, 22:52 IST

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Fat stem cells may help treat kidney ailments

Stem cells have the potential for becoming different kinds of tissue, but certain characteristics -- stiffness, viscosity, size -- are telltale signs of what they're optimized to become. Credit: Darling Lab/Brown University

To become better healers, tissue engineering need a timely and reliable way to obtain enough raw materials: cells that either already are or can become the tissue they need to build. In a new study, Brown University biomedical engineers show that the stiffness, viscosity, and other mechanical properties of adult stem cells derived from fat, such as liposuction waste, can predict whether they will turn into bone, cartilage, or fat.

That insight could lead to a filter capable of extracting the needed cells from a larger and more diverse tissue sample, said Eric Darling, senior author of the paper published in Proceedings of the National Academy of Sciences. Imagine a surgeon using such a filter to first extract fat from a patient with a bone injury and then to inject a high concentration of bone-making stem cells into the wound site during the same operation.

In the paper, the researchers report that the stiffest adipose-derived mesenchymal stem cells tended to become bone, the ones that were biggest and softest tended to become fat, and those that were particularly viscous were most likely to end up as cartilage.

"The results are exciting because not only do the mechanical properties indicate what lineage these cells could potentially go along but also the extent of their differentiation," said Darling, assistant professor of medical science in the Department of Molecular Pharmacology, Physiology. and Biotechnology and the University's Center for Biomedical Engineering. "It tells us how good they are going to be if we differentiated them for a given tissue type."

So when tissue engineers go looking through extracted fat for cells to create bone, for instance, they can sort through the cells looking for ones with a certain level of stiffness or greater. Whether the cells are "undifferentiated" stem cells that have made no move toward becoming a specific cell type, or ones that are already bone cells, only the ones with the requisite stiffness would make the cut. That process would yield a higher population of cells for making new bone tissue.

"Can we enrich the cell populations for cells that we want to use, whether they are totally undifferentiated cell types, partially differentiated, or completely differentiated?" Darling said. "It doesn't matter as long as it's targeted for the specific tissue application."

Darling's study, led by research assistants Rafael Gonzaelz-Cruz and Vera Fonseca, involved cloning adipose-derived adult human stem cells into 32 stem cell populations. They then poked, prodded, and measured the cells with an atomic force microscope, gaining measurements of how big they were, how sturdy they were under pressure, and how the force between them and the scope's cantilevered probe changed over time. The team found the cells exhibited a wide range of stiffness, viscosity and size.

Once they had the measurements, the researchers chemically induced the cells to differentiate and analyzed the levels of key metabolites produced by the cells as they matured a few weeks later. For each population, the metabolites indicated the relative proportion that differentiated into one tissue or another. Population 28, for example, apparently responded productively to chemical cues for producing cartilage, only somewhat well for producing bone and poorly to cues for making fat.

The key moment was when the researchers correlated each cell population's mechanical measurements with its metabolite data. Did the mechanical properties predict which populations would be the most successful in turning into bone cells or cartilage cells or fat cells? Sure enough, they did. The stiffest cell populations produced more bone. The squishiest cells were the ones that produced the most fat. The ones with the highest viscosity were the ones seemingly headed toward becoming cartilage.

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Mechanical properties of stem cells can foretell what they will become

ScienceDaily (May 21, 2012) Tissue engineers can use mesenchymal stem cells derived from fat to make cartilage, bone, or more fat. The best cells to use are ones that are already likely to become the desired tissue. Brown University researchers have discovered that the mechanical properties of the stem cells can foretell what they will become, leading to a potential method of concentrating them for use in healing.

To become better healers, tissue engineers need a timely and reliable way to obtain enough raw materials: cells that either already are or can become the tissue they need to build. In a new study, Brown University biomedical engineers show that the stiffness, viscosity, and other mechanical properties of adult stem cells derived from fat, such as liposuction waste, can predict whether they will turn into bone, cartilage, or fat.

That insight could lead to a filter capable of extracting the needed cells from a larger and more diverse tissue sample, said Eric Darling, senior author of the paper published in Proceedings of the National Academy of Sciences. Imagine a surgeon using such a filter to first extract fat from a patient with a bone injury and then to inject a high concentration of bone-making stem cells into the wound site during the same operation.

If mechanical properties of stem cells -- viscosity, stiffness, size -- predict what they will become, the next step is to develop a high-throughput testing and sorting device.In the paper, the researchers report that the stiffest adipose-derived mesenchymal stem cells tended to become bone, the ones that were biggest and softest tended to become fat, and those that were particularly viscous were most likely to end up as cartilage.

"The results are exciting because not only do the mechanical properties indicate what lineage these cells could potentially go along but also the extent of their differentiation," said Darling, assistant professor of medical science in the Department of Molecular Pharmacology, Physiology. and Biotechnology and the University's Center for Biomedical Engineering. "It tells us how good they are going to be if we differentiated them for a given tissue type."

So when tissue engineers go looking through extracted fat for cells to create bone, for instance, they can sort through the cells looking for ones with a certain level of stiffness or greater. Whether the cells are "undifferentiated" stem cells that have made no move toward becoming a specific cell type, or ones that are already bone cells, only the ones with the requisite stiffness would make the cut. That process would yield a higher population of cells for making new bone tissue.

"Can we enrich the cell populations for cells that we want to use, whether they are totally undifferentiated cell types, partially differentiated, or completely differentiated?" Darling said. "It doesn't matter as long as it's targeted for the specific tissue application."

Darling's study, led by research assistants Rafael Gonzaelz-Cruz and Vera Fonseca, involved cloning adipose-derived adult human stem cells into 32 stem cell populations. They then poked, prodded, and measured the cells with an atomic force microscope, gaining measurements of how big they were, how sturdy they were under pressure, and how the force between them and the scope's cantilevered probe changed over time. The team found the cells exhibited a wide range of stiffness, viscosity and size.

Once they had the measurements, the researchers chemically induced the cells to differentiate and analyzed the levels of key metabolites produced by the cells as they matured a few weeks later. For each population, the metabolites indicated the relative proportion that differentiated into one tissue or another. Population 28, for example, apparently responded productively to chemical cues for producing cartilage, only somewhat well for producing bone and poorly to cues for making fat.

The key moment was when the researchers correlated each cell population's mechanical measurements with its metabolite data. Did the mechanical properties predict which populations would be the most successful in turning into bone cells or cartilage cells or fat cells? Sure enough, they did. The stiffest cell populations produced more bone. The squishiest cells were the ones that produced the most fat. The ones with the highest viscosity were the ones seemingly headed toward becoming cartilage.

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Physical properties predict stem cell outcome

Osiris Therapeutics Inc said on Thursday that Canadian health regulators have approved its treatment for acute graft-versus host disease in children, making it the first stem cell drug to be approved for a systemic disease anywhere in the world.

Osiris shares rose 14 percent to $6.00 in extended trading after the news was announced.

Graft versus host disease (GvHD) is a potentially deadly complication from a bone marrow transplant, when newly implanted cells attack the patient's body. Symptoms range from abdominal pain and skin rash to hair loss, hepatitis, lung and digestive tract disorders, jaundice and vomiting.

The disease kills up to 80 percent of children affected, Osiris said. To date there have been no approved treatments for the disease. Canadian authorities approved the therapy, Prochymal, for use in children who have failed to respond to steroids.

Prochymal was approved with the condition that Osiris carry out further testing after it reaches the market. C. Randal Mills, the company's chief executive, said in an interview that could take three to four years.

Some investment analysts have been skeptical about Prochymal's future. In 2009, two late-stage clinical trials failed to show the drug was more effective overall than a placebo in treating the disease, though it showed promise in certain subgroups of patients.

Since then, the company has mined data from all its clinical trials to show that in patients with severe refractory acute GvHD -- those who have more or less failed all other therapies -- Prochymal demonstrated a clinically meaningful response at 28 days after therapy began in 61-64 percent of patients.

In addition, treatment with Prochymal resulted in a statistically significant improvement in survival when compared with a historical control population of pediatric patients with refractory GvHD.

The Canadian authorities approved the drug on the basis of that data, the company said.

FDA submission this year

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First stem cell drug approved for systemic disease treatment

EXTON, Pa.--(BUSINESS WIRE)--

Fibrocell Science, Inc. (OTCBB: FCSC.OB - News) announced today that it has signed an exclusive license agreement with The Regents of the University of California, under which it acquired the rights to commercially apply discoveries resulting from the scientific collaboration between the University of California, Los Angeles (UCLA) and Fibrocell Science, Inc. This is the second collaboration between Fibrocell Science and UCLA. As part of the existing agreement, using Fibrocell Sciences proprietary technology, UCLA researchers discovered rare stem cells and cell types with regenerative properties within adult human skin. These breakthrough research findings were recently published in the inaugural issue of BioResearch Open Access (May 2, 2012). The new license agreement sets the stage for the continuation of the collaboration and the development of future clinical research programs that may lead to new personalized therapies or diagnostic tools for a variety of diseases and conditions.

Fibrocell Science is looking forward to advancing and continuing our successful, long term relationship with The Regents of the University of California and UCLA. Already, our scientific collaboration with UCLA has produced exciting results that point to outstanding possibilities in the field of personalized, regenerative medicine, said David Pernock, Fibrocell Science Chairman and CEO.

The license agreement pertains to research led by James A. Byrne, Ph.D., an Assistant Professor in UCLAs Department of Molecular and Medical Pharmacology at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. His recent research published in BioResearch Open Access was related to two subtypes of cells: SSEA3-expressing regeneration-associated (SERA) cells, which may play a role in the regeneration of human tissue in response to injury, and adult mesenchymal stem cells (MSCs), which are under investigation by many independent researchers for their ability to differentiate into cells that can form bone, fat and cartilage. Finding these specialized cells within skin cell cultures is important because rather than undergoing a surgical organ or tissue transplantation to replace diseased or destroyed tissue, patients may one day be able to benefit from procedures by which stem cells are extracted from their skin, differentiated into specific cell types and re-implanted into their bodies to exert a therapeutic effect. Research in this area is ongoing.

The license agreement went into effect onMay 3, 2012and unless terminated earlier, is in effect until the last-to-expire licensed patent. As part of the ongoing collaboration with Fibrocell Science, Dr. Byrne will continue to lead the investigational team at UCLA and in his role as a scientific advisor to the company.

Fibrocell Science has also signed a sponsored research agreement with the Massachusetts Institute of Technology (MIT) to progress the research currently underway at UCLA. Under the agreement, MIT researchers will investigate viable techniques to maintain the same subpopulations of dermal cells, produce clinically meaningful quantities and deliver them to the body. The research will be led by Professor Daniel Anderson, PhD, who has a dual appointment in the Department of Chemical Engineering and the Harvard-MIT Division of Health Sciences & Technology. The sponsored research agreement with MIT also went into effect on May 3, 2012 and will end on June 30, 2015, unless the agreement is extended in the future.

About Fibrocell Science, Inc. Technology

Fibrocell Science has developed an innovative technology to isolate, purify and multiply a patients own fibroblast cells (a type of skin cell that makes collagen) for injection. Initially, this patented, proprietary technology was applied for use via the companys first product on the market, LAVIV (azficel T). The technology is also being used by Dr. Byrne and his research team at UCLA to study the composition of skin tissue samples to identify, isolate, purify and multiply specialized cell types as reported in BioResearch Open Access.

About Fibrocell Science, Inc.

Fibrocell Science, Inc. (OTCBB:FCSC.OB) is an autologous cellular therapeutic company focused on the development of innovative products for aesthetic, medical and scientific applications. Fibrocell Science is committed to advancing the scientific, medical and commercial potential of autologous skin and tissue, as well as its innovative cellular processing technology and manufacturing excellence. For additional information, please visit http://www.fibrocellscience.com.

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Fibrocell Science, Inc. Announces Exclusive License Agreement with UCLA on Dermal Cell Research to Advance the ...

SEBASTIAN Toby, a 6-year-old golden retriever, loves to run and play catch. And Oreo, a 12-year-old border collie mix, also is a bundle of energy.

Movement for both dogs got easier about a month ago when they received a revolutionary stem cell treatment at the Highlands Animal Hospital.

Veterinarian Marcus Kramer performed the successful transplant procedures, which were developed by Kentucky-based MediVet-America.

Both dogs had been in significant pain with a restricted range of motion, as shown on X-rays.

"It's made a big difference," said Kramer. "The really amazing thing is that they both healed so quickly. Both dogs had problems with their hips and were suffering from osteoarthritis. Just 30-days later, they are able to walk and run again."

Adult animal stem cell technology uses the pet's own regenerative healing power to treat dogs, cats and horses suffering from arthritis, hip dysplasia and tendon, ligament and cartilage injuries. Under anesthesia, Kramer removed about 40 grams of fat from each dog and separated the stem cells from the fat. He then activated the stem cells under an LED light, and injected them back into the dogs.

Stem cell therapy allows an animal to get off pain and anti-inflammatory drugs, Kramer said. MediVet-America's therapy is done entirely at the animal hospital in about three hours, and costs about $1,800 for dogs and $2,400 for horses. That compares to thousands of dollars that pet owners could expect to pay for medication over a pet's lifetime.

Erica Kent, a spokesman for MediVet-America, said using the LED light is integral to the patented-process, because the light helps to awaken stem cells and makes them more active. The three-color light stimulates millions of dormant cells to initiate repair from the moment the cells are injected into the animal's body, according to the MediVet-America website.

The company is also offering a program that allows pet owners to bank stem cells when animals are younger to use if their pet develops illnesses like arthritis in old age.

STEM CELL THERAPY

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Sebastian veterinarian performs stem cell treatment for pets

EXTON, Pa.--(BUSINESS WIRE)--

Fibrocell Science, Inc. (OTCBB:FCSC.OB) announced today the formation of the Clinical Investigations for Dermal Mesenchymally-Obtained Derivatives (CIDMOD) Initiative (www.CIDMOD.org) in collaboration with researchers from a number of different universities across the U.S. The CIDMOD Initiative will facilitate the collaboration of scientists, clinical researchers and private entities, including Fibrocell, to secure funding that will advance clinical research programs that may one day lead to new personalized cell therapies or diagnostic tools for a variety of diseases and conditions. The group will also submit grant requests to the California Institute of Regenerative Medicine (CIRM) and seek additional funding for the development of clinical research programs that use Fibrocells deep knowledge and expertise in cell isolation, purification and expansion via use of its proprietary technology.

Fibrocell Science is excited to support the CIDMOD Initiative. We believe the future work conducted by the Initiatives members will positively impact Fibrocells overall stem cell research strategy and significantly impact the future of personalized medicine, said David Pernock, Chairman and CEO of Fibrocell Science, Inc.

Co-directors of the CIDMOD Initiative include:

About Fibrocell Science Technology

Fibrocell Science has developed an innovative technology to isolate, purify and multiply a patients own fibroblast cells (a type of skin cell that makes collagen) for injection. Initially, this patented, proprietary technology was applied for use via the companys first product on the market, LAVIV (azficel T). The technology is also being used to study the composition of skin tissue samples to identify, isolate, purify and multiply specialized dermal cell types, such as mesenchymal stem cells (MSCs) and SSEA3-expressing regeneration-associated (SERA) cells. SERA cells may play a role in the regeneration of human skin in response to injury, and MSCs are being investigated for their ability to differentiate into cells that can form bone, cartilage and fat. Finding these specialized cells within skin cell cultures is important because rather than undergoing a surgical organ or tissue transplantation to replace diseased or destroyed tissue, patients may one day be able to benefit from procedures by which stem cells are extracted from their skin, differentiated into specific cell types, and re-implanted into their bodies to exert a therapeutic effect.

About Fibrocell Science, Inc.

Fibrocell Science, Inc. (OTCBB:FCSC.OB) is an autologous cellular therapeutic company focused on the development of innovative products for aesthetic, medical and scientific applications. Fibrocell Science is committed to advancing the scientific, medical and commercial potential of autologous skin and tissue, as well as its innovative cellular processing technology and manufacturing excellence. For additional information, please visit http://www.fibrocellscience.com.

Forward-Looking Statements

All statements in this press release that are not based on historical fact are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and the provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements include, without limitation, whether the Initiative will be successful in securing funding, and whether future work conducted by the Initiatives members will positively impact Fibrocells overall stem cell research strategy and significantly impact the future of personalized medicine. While management has based any forward-looking statements contained herein on its current expectations, the information on which such expectations were based may change. These forward-looking statements rely on a number of assumptions concerning future events and are subject to a number of risks, uncertainties, and other factors, many of which are outside of the Company's control, that could cause actual results to materially differ from such statements. Such risks, uncertainties, and other factors include, but are not necessarily limited to, those set forth under Item 1A "Risk Factors" in the Company's Annual Report on Form 10-K for the year ended December 31, 2011, as updated in "Item 1A. Risk Factors" in the Company's Quarterly Reports on Form 10-Q filed since the annual report. The Company operates in a highly competitive and rapidly changing environment, thus new or unforeseen risks may arise. Accordingly, investors should not place any reliance on forward-looking statements as a prediction of actual results. The Company disclaims any intention to, and undertakes no obligation to, update or revise any forward-looking statements. Readers are also urged to carefully review and consider the other various disclosures in the Company's public filings with the SEC.

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Fibrocell Science, Inc. and Top University Investigators Form Scientific Initiative to Assist in Securing Grant ...

Animal stem cell regenerative therapy is the newest service at the Animal Hospital of Tiffin.

"We are the official first site for the therapy in Ohio," said veterinarian Bob McClung.

The technology uses an adult animal's stem cells to heal itself.

Veterinarian Mike Brothers performed the surgery Monday on his dog, Tucker, a 2-year-old labrador retriever. It was the second surgery performed at the clinic.

Brothers said his dog's joint problems are hereditary and he's had problems since he was a puppy.

"What we've been able to do is slow down the arthritis," Brothers said. The cause of the degeneration will continue, but the fatty tissue removed from the dog can be used for future treatments.

From a piece of fatty tissue of the size removed from Tucker, McClung estimated $3.2 billion stem cells were harvested.

Each injection uses about 90 million cells, so there will be enough of the material for future treatments.

"We have basically 2 billion cells to bank," he said. "We use cryo-preservation."

In the freezing process, the cells are gradually cooled to prevent damage and stored in liquid nitrogen at temperatures of minus 80 to minus 90 degrees Fahrenheit.

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Vet undertakes stem cell surgery

Cell surface protein blows potent cells cover; targeted drug works in preclinical tests

Newswise HOUSTON Breast cancer stem cells wear a cell surface protein that is part nametag and part bulls eye, identifying them as potent tumor-generating cells and flagging their vulnerability to a drug, researchers at The University of Texas MD Anderson Cancer Center report online in Journal of Clinical Investigation.

Weve discovered a single marker for breast cancer stem cells and also found that its targetable with a small molecule drug that inhibits an enzyme crucial to its synthesis, said co-senior author Michael Andreeff, M.D., Ph.D., professor in MD Andersons Departments of Leukemia and Stem Cell Transplantation and Cellular Therapy.

Andreeff and colleagues are refining the drug as a potential targeted therapy for breast cancer stem cells, which are thought to be crucial to therapy resistance, disease progression and spread to other organs.

Its been difficult to identify cancer stem cells in solid tumors, Andreeff said. And nobody has managed to target these cells very well.

The marker is the cell surface protein ganglioside GD2. The drug is triptolide, an experimental drug that Andreeff has used in preclinical leukemia research. The team found triptolide blocks expression of GD3 synthase, which is essential to GD2production.

Triptolide stymied cancer growth in cell line experiments and resulted in smaller tumors and prolonged survival in mouse experiments. Drug development for human trials probably will take several years.

Cancer stem cells are similar to normal stem cells

Research in several types of cancer has shown cancer stem cells are a small subpopulation of cancer cells that are capable of long-term self-renewal and generation of new tumors. More recent research shows they resist treatment and promote metastasis.

Cancer stem cells are similar to normal stem cells that renew specialized tissues. The breast cancer findings grew out of Andreeffs long-term research in mesenchymal stem cells, which can divide into one copy of themselves and one differentiated copy of a bone, muscle, fat or cartilage cell.

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Scientists Discover Marker to Identify, Attack Breast Cancer Stem Cells

Chimp receives stem cells 25-year-old chimp received treatments for a torn ...

Photo by Eric Hasert

ERIC HASERT/TREASURE COAST NEWSPAPERS Dr. Darrell Nazareth, of the Florida Veterinary League in Vero Beach (background) injects chimpanzee stem cells with the help of veterinarian Dr. Jocelyn Bezner, of Save the Chimps, into the knee of Angie, a 25-year-old female chimp suffering from a torn anterior cruciate ligament, at the Save The Chimps Sanctuary in Fort Pierce. The surgery was performed inside the sanctuary's mobile surgical unit, which involved extraction of fat and blood cells that were transported to the Florida Veterinary League in Vero Beach to extract approximately 2.3 billion stem cells, then returning to the chimp sanctuary to finish the one-day procedure. "It feels wonderful, I can't wait to see the results two to three weeks out," Nazareth said about performing the procedure.

Photo by Eric Hasert

ERIC HASERT/TREASURE COAST NEWSPAPERS Nicole Devlin, a laboratory technician at the Florida Veterinary League in Vero Beach, works on a procedure to remove stem cells from blood and fat removed from Angie, a female chimp at Save The Chimps Sanctuary in Fort Pierce. After the stem cells were isolated, they were transported back to the chimp sanctuary in Fort Pierce to be injected back into Angie.

FORT PIERCE A 25-year-old female chimpanzee at the Save-the-Chimps sanctuary in Fort Pierce may be able to run again, thanks to a revolutionary stem cell treatment performed on Wednesday.

Angie, one of the 271 chimpanzees that live at the 150-acre sanctuary, received the cutting-edge treatment for a torn anterior cruciate ligament in her right knee, thanks to its Florida developer, Stemlogix LLC in Weston, and the Florida Veterinary League in Vero Beach.

The procedure, which normally would cost about $2,000, uses an animal's own fat to obtain adult stem cells, which are then injected into the problem area to stimulate growth of healthy cells.

Save-the-Chimps Veterinarian Dr. Linda Gregard handled the stem cell recovery procedures. Under anesthesia, fat was removed from chimp's abdomen Wednesday morning and transported to Dr. Darrell Nazareth at the Florida Veterinary League. Nazareth then isolated stem and regenerative cells from the fat, suspended them in platelet-rich plasma and transported the stem cells back to the sanctuary for the chimp's treatment.

"Hopefully, it stops the inflammation and encourages the injury to heal," said Nazareth, who has performed a similar treatment on 15 dogs and cats from his practice. He estimates that within two to three weeks, improvement will be seen in both the chimp's mobility and pain level.

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Angie the chimp undergoes revolutionary stem cell treatment | Video