StemCell Therapy

25 July 2012 Last updated at 21:04 ET By James Gallagher Health and science reporter, BBC News

The first child to have pioneering surgery to rebuild his windpipe with his own stem cells is doing well and is back in school.

Ciaran Finn-Lynch, who is now 13, had the ground-breaking surgery at London's Great Ormond Street Hospital in 2010.

Using Ciaran's own cells meant his immune system would not reject, and attack, the organ.

His surgeons said things were going well so far and that Ciaran could live the life of a normal teenager.

He was born with long-segment tracheal stenosis, which causes breathing difficulties. His lungs collapsed on the day he was born and he had major surgery to reconstruct his airways when he was six days old.

Metal tubes were used to hold his airways open, but in 2009 one caused huge amounts of bleeding when it damaged the main blood vessel coming out of the heart.

It was at this stage surgeons tried a pioneering operation. Instead of growing a new windpipe, they took a donor windpipe and stripped it of all the donor's cells. What was left was a three-dimensional web of collagen fibres which was transplanted into Ciaran.

Meanwhile, stem cells, which can become any other type of cell, from nerve to skin cells, were taken from Ciaran's bone marrow. These were then sprayed onto the newly transplanted windpipe.

The surgery had been tried once before in Spain, in 2008, on a 30-year-old woman, but Ciaran was the first child.

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Stem-cell op child 'doing well'

MOBILE, Alabama -- Adult stem cells extracted during liposuction can be used to grow healthy new small-diameter blood vessels for use in heart bypass surgery and other procedures, new research shows.

The findings were presented today at the American Heart Association's Basic Cardiovascular Sciences 2012 Scientific Sessions in New Orleans.

The reason that's important, health officials said, is because millions of cardiovascular disease patients are in need of small-diameter vessel grafts for procedures requiring blood to be routed around blocked arteries.

These liposuction-derived vessels, grown in a lab, could help solve major problems associated with grafting blood vessels from elsewhere in the body or from using artificial blood vessels that are not living tissue, said Matthias Nollert, Ph.D., the lead author of the study, in a written statement.

Now, Nollert said, "small-diameter vessel grafts carry an inherent risk of clotting, being rejected or otherwise failing to function normally."

Nollert said the engineered blood vessels have good mechanical properties and "we believe they will contract normally when exposed to hormones. They also appear to prevent the accumulation of blood platelets -- a component in blood that causes arteries to narrow."

Here's how it works:

In the study, according to the American Heart Association, adult stem cells derived from fat are turned into smooth muscle cells in a laboratory, and then "seeded" onto a very thin collagen membrane.

As the stem cells multiplied, the researchers rolled them into tubes matching the diameter of small blood vessels. In three to four weeks, they grew into usable blood vessels.

Creating blood vessels with this technique has the potential for "off-the-shelf" replacement vessels that can be used in graft procedures, Nollert said.

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Stem cells from fat used to grow blood vessels in lab, research shows

In a Tissue-Engineering First, Doctors Think the Boy's New Windpipe Could Grow

July 25, 2012 -- Ciaran Finn-Lynch is an accidental medical pioneer. With his life in danger, doctors used the 13-year-old's own stem cells to grow him a new windpipe, and they did it inside his body -- a feat that's never been accomplished before.

"It's a really heroic story," says Harald C. Ott, MD, an instructor of medicine at Harvard Medical School in Boston. "They really saved this kid's life."

Ott worked out some of the science that made the procedure possible but was not directly involved in Ciaran's treatment.

Two years after the surgery, doctors say Ciaran (pronounced KEER-an) is living the life of a normal teen. He's grown more than 4 inches and gone back to school. Best of all, he has no need for an expensive and complicated regimen of anti-rejection drugs.

What doctors are learning from his case could help thousands of children born each year with life-threatening birth defects.

Ciaran was born with a windpipe so small and deformed that it caused his lungs to collapse.

Doctors managed to hold his airway open using metal tubes. But eventually the tubes eroded into his aorta, the large vessel that carries blood out of the heart. He was rushed to the hospital with massive bleeding. Twice.

The second time, the bleeding stopped on its own. That gave his doctors a small window of time to look for other options.

Two years earlier, scientists had devised a new way to create organs using a patient's own stem cells. Though the technique had only been tried in adults, they thought the same method might work for Ciaran.

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Doctors Report Historic Transplant in Child

Scientists have turned back the hands of a biological clock to rejuvenate ageing and damaged human heart cells.

Using stem cells, they reset a molecular mechanism that determines the rate at which cells age.

Although the work on human cells was confined to the laboratory, the same technique has been successfully tested in mice and pigs.

Researchers in the US managed to get new heart tissue to grow in the animals in just four weeks.

They hope the advance will lead to new treatments for heart failure, which often follows a heart attack.

'Modifying aged human cardiac cells from elderly patients adds to the cell's ability to regenerate damaged heart muscle, making stem cell engineering a viable option,' said lead scientist Dr Sadia Mohsin, from San Diego State University in California.

During heart failure the damaged heart is not strong enough to pump blood around the body efficiently, leading to rapid exhaustion.

In the laboratory studies, Dr Mohsin's team worked on heart tissue surgically removed from elderly patients.

Stem cells from the samples were treated with a growth protein called PIM-1.

The effect was to boost activity of an enzyme called telomerase, which has a direct impact on ageing.

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Breakthrough on damaged heart cells

Public release date: 24-Jul-2012 [ | E-mail | Share ]

Contact: Nicole Fawcett nfawcett@umich.edu 734-764-2220 University of Michigan Health System

The finding involves the cancer gene RhoC, which has previously been shown to promote metastasis of many types of cancer. RhoC levels increase as breast cancer progresses and high levels of RhoC are associated with worse patient survival.

Cancer stem cells are the small number of cells within a tumor that are believed to fuel the tumor's growth and spread. Researchers believe traditional chemotherapy and radiation treatments often become ineffective because they do not kill the cancer stem cells, and that the key to future treatments is to develop drugs that target and kill these cells.

This new study, which appears online in PLoS ONE, suggests a new way to get at the cancer stem cells.

"Targeting the specific molecular cogs driving the cancer stem cell machinery responsible for the cancer spreading has potential for future treatments. Eliminating cancer stem cells may ultimately be necessary to cure certain cancers, but in the meantime, we may be able to manage the cancer stem cell population and the invasive behaviors of these cells by disrupting the molecular machinery, using RhoC as a target," says senior study author Sofia D. Merajver, M.D., Ph.D., professor of internal medicine and epidemiology at the University of Michigan and scientific director of the breast oncology program at the U-M Comprehensive Cancer Center.

The researchers looked at breast cancer cell lines that were highly metastatic and cell lines from normal breast tissue. By inhibiting or overexpressing RhoC, they found that RhoC expression is necessary to cause metastasis in both cell lines, and that RhoC overexpression alone can cause metastasis. The researchers also tested this in mice and had similar results.

Merajver's lab, in conjunction with other U-M researchers, is studying a novel small molecule drug to inhibit RhoC, which has shown promising initial results in the laboratory. The researchers are continuing to develop this inhibitor, which will require several years of additional testing in the laboratory before potentially advancing to clinical trials.

Breast cancer statistics: 229,060 Americans will be diagnosed with breast cancer this year and 39,920 will die from the disease, according to the American Cancer Society

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Researchers find driver of breast cancer stem cell metastasis

NEW ORLEANS, July 23 (UPI) -- U.S. scientists said they modified stem cells that rejuvenated damaged and aged heart tissue in older heart failure patients.

Sadia Mohsin, a postdoctoral research scholar at San Diego State University's Heart Institute, said the finding could one day lead to new treatments for heart failure patients.

Modified human stem cells helped the signaling and structure of the heart cells, which were biopsied from elderly patients, Mohsin explained.

The researchers modified the stem cells in the laboratory with PIM-1 -- a protein that promotes cell survival and growth, Mohsin said.

Cells were rejuvenated when the modified stem cells enhanced activity of the enzyme telomerase, which elongates telomere length. Telomeres are "caps" on the ends of chromosomes that facilitate cell

replication. Aging and disease results when telomeres break off.

"There is no doubt that stem cells can be used to counter the aging process of cardiac cells caused by telomere degradation," Mohsin said in a statement.

The technique increased telomere length and activity, and increased cardiac stem cell proliferation, all vital steps in combating heart failure, Mohsin told the American Heart Association's Basic Cardiovascular Sciences scientific sessions.

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Heart rejuvenated with modified stem cells

ScienceDaily (July 24, 2012) Researchers at the University of Michigan Comprehensive Cancer Center have found that a cancer gene linked to aggressive spread of the disease promotes breast cancer stem cells. The finding implies a new way to target the behavior of these lethal cells.

The finding involves the cancer gene RhoC, which has previously been shown to promote metastasis of many types of cancer. RhoC levels increase as breast cancer progresses and high levels of RhoC are associated with worse patient survival.

Cancer stem cells are the small number of cells within a tumor that are believed to fuel the tumor's growth and spread. Researchers believe traditional chemotherapy and radiation treatments often become ineffective because they do not kill the cancer stem cells, and that the key to future treatments is to develop drugs that target and kill these cells.

This new study, which appears online in PLoS ONE, suggests a new way to get at the cancer stem cells.

"Targeting the specific molecular cogs driving the cancer stem cell machinery responsible for the cancer spreading has potential for future treatments. Eliminating cancer stem cells may ultimately be necessary to cure certain cancers, but in the meantime, we may be able to manage the cancer stem cell population and the invasive behaviors of these cells by disrupting the molecular machinery, using RhoC as a target," says senior study author Sofia D. Merajver, M.D., Ph.D., professor of internal medicine and epidemiology at the University of Michigan and scientific director of the breast oncology program at the U-M Comprehensive Cancer Center.

The researchers looked at breast cancer cell lines that were highly metastatic and cell lines from normal breast tissue. By inhibiting or overexpressing RhoC, they found that RhoC expression is necessary to cause metastasis in both cell lines, and that RhoC overexpression alone can cause metastasis. The researchers also tested this in mice and had similar results.

Merajver's lab, in conjunction with other U-M researchers, is studying a novel small molecule drug to inhibit RhoC, which has shown promising initial results in the laboratory. The researchers are continuing to develop this inhibitor, which will require several years of additional testing in the laboratory before potentially advancing to clinical trials.

Breast cancer statistics: 229,060 Americans will be diagnosed with breast cancer this year and 39,920 will die from the disease, according to the American Cancer Society

Additional authors: Devin T. Rosenthal, Jie Zhang, Liwei Bao, Lian Zhu, Zhifen Wu, Kathy Toy and Celina G. Kleer, all from U-M

Funding: Department of Defense Breast Cancer Research Program (BC083262); National Institutes of Health (T32-GM07315); Burroughs Wellcome Fund; Breast Cancer Research Foundation

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Driver of breast cancer stem cell metastasis found

StemCells Inc. hopes a clinical trial of its proprietary stem cells in rodents will lead to a clinical trial with Alzheimer's patients.

Neurosphere: StemCells is testing neuronal stem cells, which form floating aggregates when grown in culture, as a treatment for Alzheimers disease, spinal cord injury, and other neurological conditions. StemCells Inc.

Last week, a California biotech company announced that its human stem cells restored memory in rodents bred to have an Alzheimer's-like conditionthe first evidence that human neural stem cells can improve memory.

The company, called StemCells, is betting that its proprietary preparation of stem cells from fetal brain tissue will take on many different roles in the central nervous system. The company and its collaborators have already shown that its stem-cell product has potential in protecting vision in diseased eyes, acting as brain support cells, or improving walking ability in rodents with spinal cord injury.

This metamorphic ability is not so surprisingthey are stem cells, after all. But experts say the quality of scientists involved in StemCells and the interesting properties of its cells sets the company apart. "They've really been steadfast in their work to get these cells into clinical trials. That is a tough road and they've done it," says Larry Goldstein, a neuronal stem-cell researcher and director of UC San Diego's stem-cell program.

The company discovered the technique to isolate these cells from brain tissue in 1999 and has since spent some $200 million improving the technology. "Now we are really in the exciting phase, because now we are looking at human clinical data, as opposed to just small animals," says StemCells CEO Martin McGlynn.

His company is not the only group bringing stem cells into the clinic. While much attention was paid to Geron's departure from the world's first embryonic stem cell trial (see "Geron Shuts Down Pioneering Stem-Cell Program"), many other groups have continued to push their non-embryonic stem-cell therapies forward for leukemia, colitis, stroke, and more. Meanwhile, Advanced Cell Technology continues its U.K.-based embryonic stem-cell therapy trials for blindness. Non-embryonic stem cells can come from a variety of sourcesbone marrow, blood, as well as donated aborted fetal tissue, as is the case with StemCells and Neuralstem, another company focused on neuronal stem cells. In recent years, scientists have also developed methods for turning normal adult cells into stem cells (so-called induced pluripotent stem cells), but their safety has yet to be tested in humans.

So while StemCells is not a lone wolf, it may well be a pack leader. One of StemCells' first human studies involved a small trial of young children with a rare and fatal neurodegenerative disease called Batten disease. In 2006, the company began the first U.S. Food and Drug Administration-authorized trial of human neural stem cells at Oregon Health and Science University. Through small boreholes in the skull, a neurosurgeon implanted as many as a billion neural stem cells into different locations of the brains of six Batten patients.

The trial has since suggested that the cells are safe and integrate into the brain. At first, the children received immune system-suppressing drugs to prevent their body from rejecting the cells. But after a year, that treatment was stopped. "A big question that we had, that science had, that the FDA had, was what happens to these cells when you withdraw immunosuppression?" says McGlynn.

The treatment, however, did not rescue the children from the effects of the disease, and some have since succumbed to the disorder. Some of the parents of the children who passed away gave permission for an autopsy, enabling the scientists to see that even after one and a half years with no immunosuppression, the transplanted cells had survived. The company wanted to try the cellular therapy in children at an earlier stage of the disease, but was unable to find eligible patients at such a point in the disease course and canceled the trial.

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Human Stem Cells Found to Restore Memory

WALTHAM, Mass.--(BUSINESS WIRE)--

Regenerative medicine company Histogenics Corporation, announced today the completion of a $49 million round of financing. The syndicate was led by Sofinnova Ventures with participation from additional new investors Split Rock Partners, BioMed Ventures and FinTech GIMV Fund, L.P. Existing investors ProChon Holdings BV, Altima Partners, Foundation Medical Partners, Inflection Point Capital and Boston Millennia Partners also participated in the financing. Proceeds will be used to complete the ongoing Phase 3 clinical program for lead product candidate NeoCart, which is currently enrolling patients. NeoCart is an autologous neocartilage tissue implant that utilizes the patients own cells to regenerate cartilage in patients suffering from cartilage lesions in the knee. Funds will also support efforts to obtain regulatory clearance in the European Union for product candidate VeriCart, a single-step, cell-free collagen scaffold uniquely designed to be used in conjunction with the patients own stem cells, to repair small cartilage defects frequently observed in meniscal and anterior cruciate ligament repair procedures. Garheng Kong, MD, PhD of Sofinnova Ventures and Josh Baltzell of Split Rock Venture Partners will join Histogenics Board of Directors. Arnold Freedman of Boston Equity Advisors served as the exclusive placement agent.

Patrick ODonnell, President and Chief Executive Officer of Histogenics, commented, We believe the quality of the investors and the significant level of commitment demonstrated in this financing speak to the potential of our product candidates to transform the treatment of cartilage injury with the goal of returning patients to their pre-injury level of activity. Each year, 1.8 million active adults and elite athletes undergo arthroscopy for the diagnosis and treatment of painful cartilage defects in the knee. With continued positive clinical results, we believe our Phase 3 product candidate, NeoCart, has considerable potential as a much-needed treatment alternative for a significant portion of these patients. The successful completion of this financing fully funds the Company to reach key clinical and commercial milestones for NeoCart and VeriCart and allows us to focus our full attention on continued successful clinical and regulatory execution.

Garheng Kong, MD, PhD, General Partner of Sofinnova Ventures added, NeoCart has the potential to dramatically change the way knee cartilage injuries are treated. Current treatments for knee cartilage damage frequently do not produce the lasting effects that individuals need to avoid serious knee pain and improve functionpreventing them from getting back to their active, daily lives. Published data have shown that patients treated with NeoCart experienced a very durable response that is sustained throughout a period of four years or more. Sofinnova is pleased to support Histogenics efforts to receive approval for NeoCart and address this unmet clinical need.

About NeoCart NeoCartis an autologous bioengineered neocartilage grown outside the body using the patients own cells for the regeneration of cartilage lesions. NeoCart recently entered a Phase 3 clinical trial after reporting positive Phase 2 data, in which all primary endpoints were met, and NeoCart was found to be generally well tolerated.

About VeriCart VeriCart is a single step, off-the-shelf, cell-free collagen scaffold, specifically designed for cartilage applications, which when reconstituted with the patients own bone marrow or augmenting marrow stimulation procedures, is intended for the improved repair of cartilage tissue. VeriCart is currently in development.

About Histogenics Histogenics is a leading regenerative medicine company that combines cell therapy and tissue engineering technologies to develop highly innovative products for tissue repair and regeneration. In May of 2011, Histogenics acquired Israeli cell-therapy company ProChon BioTech. Histogenics flagship products focus on the treatment of active patients suffering from articular cartilage derived pain and immobility. The Company takes an interdisciplinary approach to engineering neocartilage that looks, acts and lasts like hyaline cartilage. It is developing new treatments for sports injuries and other orthopedic conditions, where demand is growing for long-term alternatives to joint replacement. Histogenics has successfully completed Phase 1 and Phase 2 clinical trials in which the NeoCart autologous tissue implants effectiveness is compared to that of standard microfracture surgery. Based in Waltham, Massachusetts, the company is privately held. For more information, visitwww.histogenics.com.

About Sofinnova Ventures Sofinnova Ventures has over 40 years of experience building start-ups and later stage companies into market leaders. With $1.4 billion under management, the firm applies capital and expertise to build companies from inception to exit. Sofinnova closed its life science-focused $440M, SVP VIII, in late 2011. The firms investment team of MDs and PhDs has significant scientific, operational and strategic experience, and specializes in financing later stage clinical products. The Sofinnova team partners with entrepreneurs to address patients unmet medical needsand has had a string of recent exits through companies, including Movetis, Preglem, Amarin, Vicept and Intellikine.

About Split Rock Partners Split Rock Partners, with offices in Minneapolis and Menlo Park, seeks emerging opportunities in healthcare as well as software and internet services. Since 2005, Split Rock has raised $575 million over two funds. Representative companies backed by Split Rock's team include Ardian, Atritech, DFine, Entellus, eBureau, Evalve, Guardian Analytics, HireRight, Intacct, LowerMyBills, MyNewPlace, QuinStreet (QNST), SPS Commerce (SPSC) and Tornier (TRNX). Additional information about the firm can be found atwww.splitrock.com.

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Histogenics Closes $49 Million Series A Fundraising to Support Commercial Development of Transformational Cartilage ...

Public release date: 24-Jul-2012 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, July 24, 2012A naturally occurring line of immunodeficient pigs can support the growth of human tumors injected under their skin, offering a promising new large animal model for studying human cancers and testing new drugs and treatment strategies. The ability of human melanoma cells and pancreatic carcinoma cells to grow in these pig models is described in an article in BioResearch Open Access, a new bimonthly peer-reviewed open access journal from Mary Ann Liebert, Inc. (http://www.liebertpub.com). The article is available free online at the BioResearch Open Access website (http://www.liebertpub.com/biores).

Mathew Basel and colleagues, Kansas State University (Manhattan, KS) and Iowa State University (Ames), highlight the advantages that pig disease models offer, as they are anatomically and physiologically more closely related to humans than traditional rodent animal models. As a result, findings from studies in large animal models such as pigs are more likely to translate into similar outcomes in humans. The authors present their findings in the article "Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs" (http://online.liebertpub.com/doi/full/10.1089/biores.2012.9902).

"This novel animal model has the potential to become a highly useful model in cancer research studies, in addition to providing significant opportunities for drug discovery and other translational applications," says Editor-in-Chief Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland.

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About the Journal

BioResearch Open Access (http://www.liebertpub.com/biores) is a bimonthly peer-reviewed open access journal that provides a new rapid-publication forum for a broad range of scientific topics including molecular and cellular biology, tissue engineering and biomaterials, bioengineering, regenerative medicine, stem cells, gene therapy, systems biology, genetics, biochemistry, virology, microbiology, and neuroscience. All articles are published within 4 weeks of acceptance and are fully open access and posted on PubMedCentral. All journal content is available online at the BioResearch Open Access website (http://www.liebertpub.com/biores).

About the Publisher

Mary Ann Liebert, Inc., publishers (http://www.liebertpub.com) is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Stem Cells and Development, Human Gene Therapy and HGT Methods, and AIDS Research and Human Retroviruses. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc. website (http://www.liebertpub.com).

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Novel pig model may be useful for human cancer studies

NEW YORK, NY--(Marketwire -07/24/12)- The Biotechnology Industry has been soaring in 2012 as companies -- both large and small -- have shown impressive growth. The SPDR S&P Biotech ETF (XBI) and the First Trust NYSE Arca Biotech Index ETF (FBT) year-to-date are up 38 percent and 37 percent, respectively, outperforming the broader market by a wide margin. The Paragon Report examines investing opportunities in the Biotechnology Industry and provides equity research on StemCells, Inc. (STEM) and Keryx Biopharmaceuticals (KERX).

Access to the full company reports can be found at:

http://www.ParagonReport.com/STEM http://www.ParagonReport.com/KERX

Despite having to negotiate a more challenging regulation process biotech companies have continued to show investors strong gains in 2012. The FDA Amendments Act of 2007 forced regulators to increase standards for approvals of new drugs, introducing mandatory risk evaluation and mitigation strategies. According to a Pharmaceuticals & Biotechnology report from IMAP, several pharmaceutical firms have altered their drug portfolios from primary care driven blockbusters towards specialties such as oncology, immunology and inflammation, where the medical need is "so high that prices are more easily accepted by the regulators."

Paragon Report releases regular market updates on the Biotechnology Industry so investors can stay ahead of the crowd and make the best investment decisions to maximize their returns. Take a few minutes to register with us free at http://www.ParagonReport.com and get exclusive access to our numerous stock reports and industry newsletters.

StemCells is engaged in the research, development, and commercialization of cell-based therapeutics and tools for use in stem cell-based research and drug discovery. The company recently announced preclinical data demonstrating that its proprietary human neural stem cells restored memory and enhanced synaptic function in two animal models relevant to Alzheimer's disease. Shares of the company have soared nearly 90 percent this year.

Keryx Biopharmaceuticals is focused on the acquisition, development and commercialization of medically important pharmaceutical products for the treatment of renal disease. Keryx is developing Zerenex (ferric citrate), an oral, ferric iron-based compound that has the capacity to bind to phosphate and form non-absorbable complexes. Shares of the company have rebounded nearly 50 percent over the last three months.

The Paragon Report has not been compensated by any of the above-mentioned publicly traded companies. Paragon Report is compensated by other third party organizations for advertising services. We act as an independent research portal and are aware that all investment entails inherent risks. Please view the full disclaimer at: http://www.paragonreport.com/disclaimer

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StemCells and Keryx Biopharmaceuticals Showing Strong Gains as Biotechnology Industry Soars in 2012

ScienceDaily (July 23, 2012) Stem cells hold great promise for the medicine of the future, but they can also be a cause of disease. When these self-renewing, unspecialized cells fail to differentiate into diverse cell types, they can start dividing uncontrollably, leading to cancer. Already several decades ago, Weizmann Institute scientists were among the first to demonstrate the link between cancer and the faulty differentiation of stem cells. Now a new Weizmann Institute-led study, published in Molecular Cell, reveals a potential molecular mechanism behind this link.

The scientists managed to uncover the details of a step in the process of DNA "repackaging" that takes place during embryonic stem cell differentiation. It turns out that for the cells to differentiate properly, certain pieces of the packaging of their DNA must be labeled by a molecular tag called ubiquitin. Such tagging is required for turning on a group of particularly long genes, which enable the stem cell to differentiate. The researchers identified two switches: An enzyme called RNF20 enhances the tagging, whereas a second enzyme, USP44, does the opposite, shutting it down. Furthermore, it appears that both these switches must operate properly for the differentiation process to proceed efficiently. When the scientists interfered with the tagging -- either by disabling the "ON" switch RNF20, or by deregulating the activity of the "OFF" switch USP44 -- the stem cells failed to differentiate.

These experiments might explain the significance of molecular defects identified in a number of cancers, for example, the abnormally low levels of RNF20 in certain breast and prostate cancers and the excess of USP44 in certain leukemias. Notably, faulty differentiation of stem cells is often a hallmark of the more aggressive forms of cancer. This research was led by Prof. Moshe Oren of the Molecular Cell Biology Department, with Prof. Eytan Domany of the Physics of Complex Systems Department and Dr. Jacob Hanna of the Molecular Genetics Department. The team included Weizmann Institute's Gilad Fuchs, Efrat Shema, Rita Vesterman, Eran Kotler, Sylvia Wilder, Lior Golomb, Ariel Pribluda and Ester Feldmesser, as well as Zohar Wolchinsky of the Technion -- Israel Institute of Technology; Feng Zhang and Xiaochun Yu of the University of Michigan in the US; Mahmood Haj-Yahya and Ashraf Brik of Ben-Gurion University of the Negev; and Daniel Aberdam of the Technion and the University of Nice-Sophia Antipolis in France.

This study belongs to a relatively new direction in cancer research: Rather than focusing on the genes involved, it highlights the role of epigenetics -- that is, processes that do not modify the gene code, itself, but affect the way its information is interpreted within the cell. Understanding the epigenetic roots of cancer will advance the search for effective therapies for this disease.

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Judging DNA by its cover: Explaining the link between stem cells and cancer

Public release date: 23-Jul-2012 [ | E-mail | Share ]

Contact: Yivsam Azgad news@weizmann.ac.il 972-893-43856 Weizmann Institute of Science

Stem cells hold great promise for the medicine of the future, but they can also be a cause of disease. When these self-renewing, unspecialized cells fail to differentiate into diverse cell types, they can start dividing uncontrollably, leading to cancer. Already several decades ago, Weizmann Institute scientists were among the first to demonstrate the link between cancer and the faulty differentiation of stem cells. Now a new Weizmann Institute-led study, published in Molecular Cell, reveals a potential molecular mechanism behind this link.

The scientists managed to uncover the details of a step in the process of DNA "repackaging" that takes place during embryonic stem cell differentiation. It turns out that for the cells to differentiate properly, certain pieces of the packaging of their DNA must be labeled by a molecular tag called ubiquitin. Such tagging is required for turning on a group of particularly long genes, which enable the stem cell to differentiate. The researchers identified two switches: An enzyme called RNF20 enhances the tagging, whereas a second enzyme, USP44, does the opposite, shutting it down. Furthermore, it appears that both these switches must operate properly for the differentiation process to proceed efficiently. When the scientists interfered with the tagging either by disabling the "ON" switch RNF20, or by deregulating the activity of the "OFF" switch USP44 the stem cells failed to differentiate.

These experiments might explain the significance of molecular defects identified in a number of cancers, for example, the abnormally low levels of RNF20 in certain breast and prostate cancers and the excess of USP44 in certain leukemias. Notably, faulty differentiation of stem cells is often a hallmark of the more aggressive forms of cancer. This research was led by Prof. Moshe Oren of the Molecular Cell Biology Department, with Prof. Eytan Domany of the Physics of Complex Systems Department and Dr. Jacob Hanna of the Molecular Genetics Department. The team included Weizmann Institute's Gilad Fuchs, Efrat Shema, Rita Vesterman, Eran Kotler, Sylvia Wilder, Lior Golomb, Ariel Pribluda and Ester Feldmesser, as well as Zohar Wolchinsky of the Technion Israel Institute of Technology, Feng Zhang and Xiaochun Yu of the University of Michigan in the US, Mahmood Haj-Yahya and Ashraf Brik of Ben-Gurion University of the Negev, and Daniel Aberdam of the Technion and the University of Nice-Sophia Antipolis in France.

This study belongs to a relatively new direction in cancer research: Rather than focusing on the genes involved, it highlights the role of epigenetics that is, processes that do not modify the gene code, itself, but affect the way its information is interpreted within the cell. Understanding the epigenetic roots of cancer will advance the search for effective therapies for this disease.

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Prof. Eytan Domany's research is supported by the Kahn Family Research Center for Systems Biology of the Human Cell, which he heads; the Mario Negri Institute for Pharmacological Research - Weizmann Institute of Science Exchange Program; the Leir Charitable Foundations; and Mordechai Segal, Israel. Prof. Domany is the incumbent of the Henry J. Leir Professorial Chair.

Dr. Jacob Hanna's research is supported by the Leona M. and Harry B. Helmsley Charitable Trust; Pascal and Ilana Mantoux, France/Israel; the Sir Charles Clore Research Prize; Erica A. Drake and Robert Drake; and the European Research Council.

Prof. Moshe Oren's research is supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the Robert Bosch Foundation; the estate of Harold Z. Novak; and the European Research Council. Prof. Oren is the incumbent of the Andre Lwoff Professorial Chair in Molecular Biology.

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Judging DNA by its cover

MOBILE, Alabama -- Damaged and aged heart tissue of older heart failure patients was rejuvenated by stem cells modified by scientists, according to research presented today at the American Heart Associations Basic Cardiovascular Sciences 2012 Scientific Sessions in New Orleans.

The study is simultaneously published in the Journal of the American College of Cardiology. The stem cell research could lead to new treatments for heart failure patients, researchers said.

Since patients with heart failure are normally elderly, their cardiac stem cells arent very healthy, said Sadia Mohsin, Ph.D., one of the study authors and a post-doctoral research scholar at San Diego State Universitys Heart Institute in San Diego.

We modified these biopsied stem cells and made them healthier. It is like turning back the clock so these cells can thrive again.

Modified human stem cells helped the signaling and structure of the heart cells, which were biopsied from elderly patients, according to information provided by the American Heart Association.

Researchers modified the stem cells in the laboratory with PIM-1, a protein that promotes cell survival and growth. Cells were rejuvenated when the modified stem cells enhanced activity of an enzyme called telomerase, which elongates telomere length.

Telomeres are caps on the ends of chromosomes that aid cell replication. Aging and disease results when telomeres break off.

There is no doubt that stem cells can be used to counter the aging process of cardiac cells caused by telomere degradation, Mohsin said in a statement.

The technique increased telomere length and activity, as well as increasing cardiac stem cell proliferation, all vital steps in combating heart failure, health officials have said.

While human cells were used, the research was limited to the laboratory. Researchers have tested the technique in mice and pigs and found that telomere lengthening leads to new heart tissue growth in about four weeks.

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Stem cells used to rejuvenate damaged heart tissue, study shows

CLEARWATER, FL--(Marketwire -07/23/12)- Biostem U.S., Corporation, (HAIR) (HAIR) (Biostem, the Company), a fully reporting public company in the stem cell regenerative medicine sciences sector, enters into an agreement with Pizarro Hair Restoration Clinics to offer The Biostem Method of stem cell hair re-growth treatments.

Biostem U.S., Corporation announced today that it has entered into a contractual affiliate agreement with Dr. Marina Pizarro and her multi-location practice, Pizarro Hair Restoration Clinics http://www.DrPizarro.com. Additionally, Dr. Pizarro will serve as the Medical Director for the company.

Dr. Pizarro's Orlando, Florida office will serve as the national training center for future Biostem U.S. affiliates.

Dwight Brunoehler, Chief Executive Officer for Biostem, stated, "We have been seeking the right partner to become our first affiliate. We have also been seeking a qualified Medical Director as well as a first rate training facility to accommodate the many requests for affiliation that we have received nationwide from physicians wanting to offer our services to their clientele. The Company is extremely fortunate to have filled these multiple needs in one place. Dr. Pizarro's impeccable credentials and extensive experience rank her among the best in her field. We look forward to a long and prosperous relationship."

According to Dr. Pizarro, "I have been following the discovery and development of hair re-growth technology on the cellular level for some time. Biostem's unique approach using Platelet Rich Plasma along with other proven treatments has shown to be highly effective for many qualified male and female patients. I am excited to be able to offer this service to my patients, and to be on the ground floor of this growing industry."

Dr. Marina Pizarro holds the distinction of being the first female hair transplant physician in the industry and belongs to the elite group of surgeons who have performed over 30,000 hair transplant procedures in their careers. She received her Medical Degree from Ponce School of Medicine in Puerto Rico in 1985. After completing her residency in Orlando, Dr. Pizarro worked with world renowned hair transplant surgeon Dr. Constantine Chambers building one of the largest hair restoration practices in history. After five years, and performing thousands of procedures around the world while lecturing at hair restoration conventions, Dr. Pizarro opened her first two facilities in Orlando and Jacksonville, Florida in 1994 specializing in hair transplantation for both men and women. She currently has three facilities in Florida with the addition of her clinic in Tampa. Dr. Pizarro is a member of The International Society of Hair Restoration Surgery and the European Society of Hair Restoration Surgery.

About Biostem U.S., Corporation:

Biostem U.S., Corporation (HAIR) is a fully reporting Nevada corporation with offices in Clearwater, Florida. Biostem U.S. is a technology licensing company with proprietary technology centered on providing hair re-growth using human stem cells. The company also intends to train and license selected physicians to provide Regenerative Cellular Therapy treatments to assist the body's natural approach to healing tendons, ligaments, joints and muscle injuries by using the patient's own stem cells. Biostem U.S. is seeking to expand its operations worldwide through licensing of its proprietary technology and acquisition of existing stem cell related facilities. The company's goal is to operate in the international biotech market, focusing on the rapidly growing regenerative medicine field, using ethically sourced adult stem cells to improve the quality and longevity of life for all mankind.

The company's Board of Directors is headed by Chairman, Scott Crutchfield, who also acts as Senior Vice President of World Wide Operations for Crocs, Inc. (CROX) and includes Crocs, Inc. original member, Steve Beck.

For further information on Biostem U.S., Corporation can be obtained through http://www.biostemus.com or by contacting Fox Communications Group at 310-974-6821.

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Biostem U.S., Corporation Enters Into Medical Affiliate Agreement With Pizarro Hair Restoration Clinics

Public release date: 23-Jul-2012 [ | E-mail | Share ]

Contact: Dean Forbes dforbes@fhcrc.org 206-667-2896 Fred Hutchinson Cancer Research Center

SEATTLE Researchers at Fred Hutchinson Cancer Research Center have opened a clinical trial to test the theory that giving a patient a new immune system can cure severe cases of Crohn's disease, a chronic inflammatory condition of the gastrointestinal tract.

Funded by an infrastructure grant from The Eli and Edythe Broad Foundation, the initial goal of the Crohn's Allogeneic Transplant Study (CATS) is to treat a small number of patients with treatment-resistant Crohn's disease by transplanting matched bone marrow cells from a sibling or unrelated donor. Such a bone marrow transplant replaces a diseased or abnormal immune system with a healthy one.

The idea of swapping out the immune system is based on evidence that Crohn's is related to an abnormal immune response to intestinal bacteria and a loss of immune tolerance. There is strong evidence that genetic abnormalities in the immune regulatory system are linked to the disease, according to CATS principal investigator George McDonald, M.D., a transplant researcher and gastroenterologist in the Hutchinson Center's Clinical Research Division.

Although the CATS clinical trial represents a new direction for bone marrow transplantation, the procedure has precedent. The Hutchinson Center, which pioneered bone marrow and hematopoietic cell transplantation to treat blood cancers, has used allogeneic transplants to cure patients who suffered from both leukemia and Crohn's, with subsequent disappearance of the signs and symptoms of Crohn's. Similar experiences have been reported from studies done in Germany.

While autologous stem cell transplants in which the patient's own hematopoietic cells are removed and then returned after high-dose chemotherapy is given to suppress the immune system have been used to treat Crohn's patients, the benefits have not always been permanent, probably because the risk genes for Crohn's are still present. "Autologous transplantation following chemotherapy beats the disease down but the Crohn's tends to come back," McDonald said.

More information about CATS can be found on the website http://www.cats-fhcrc.org, which includes a patient-eligibility questionnaire. In general, patients must be 18 to 60 years of age and have failed all existing conventional treatments but be healthy enough to undergo a bone marrow transplant. A matched donor of bone marrow must be found from either a sibling or an unrelated person who has volunteered to donate marrow. Private insurance must cover the cost of the transplant and related medical expenses.

Crohn's disease is usually discovered in adolescents and young adults but can occur from early childhood to older age. The incidence of Crohn's disease varies in different parts of the world with rates of four to nine persons per 100,000 people in North America. According to the Crohn's and Colitis Foundation of America, a leading advocacy organization, Crohn's may affect more than 700,000 Americans. Of those affected by Crohn's, about 10 percent suffer from the most severe form for which no treatment is completely effective.

Symptoms of Crohn's may include pain, fever, diarrhea and weight loss. Substantial progress has been made in medical treatment of Crohn's disease over the last 15 years. However, even with the best immunosuppressive therapy, less than half of patients with moderate to severe Crohn's achieve long-term relief. When patients stop taking their medicines, their intestinal inflammation returns. Some severe infections have been seen in patients who took prolonged courses of medicines that suppress the immune system.

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Clinical trial seeks to cure advanced Crohn's disease using bone marrow transplant

Study represents new use of bone marrow transplantation

Newswise SEATTLE Researchers at Fred Hutchinson Cancer Research Center have opened a clinical trial to test the theory that giving a patient a new immune system can cure severe cases of Crohns disease, a chronic inflammatory condition of the gastrointestinal tract.

Funded by an infrastructure grant from The Eli and Edythe Broad Foundation, the initial goal of the Crohns Allogeneic Transplant Study (CATS) is to treat a small number of patients with treatment-resistant Crohns disease by transplanting matched bone marrow cells from a sibling or unrelated donor. Such a bone marrow transplant replaces a diseased or abnormal immune system with a healthy one.

The idea of swapping out the immune system is based on evidence that Crohns is related to an abnormal immune response to intestinal bacteria and a loss of immune tolerance. There is strong evidence that genetic abnormalities in the immune regulatory system are linked to the disease, according to CATS principal investigator George McDonald, M.D., a transplant researcher and gastroenterologist in the Hutchinson Centers Clinical Research Division.

Although the CATS clinical trial represents a new direction for bone marrow transplantation, the procedure has precedent. The Hutchinson Center, which pioneered bone marrow and hematopoietic cell transplantation to treat blood cancers, has used allogeneic transplants to cure patients who suffered from both leukemia and Crohns, with subsequent disappearance of the signs and symptoms of Crohns. Similar experiences have been reported from studies done in Germany.

While autologous stem cell transplants in which the patients own hematopoietic cells are removed and then returned after high-dose chemotherapy is given to suppress the immune system have been used to treat Crohns patients, the benefits have not always been permanent, probably because the risk genes for Crohns are still present. Autologous transplantation following chemotherapy beats the disease down but the Crohns tends to come back, McDonald said.

More information about CATS can be found on the website http://www.cats-fhcrc.org, which includes a patient-eligibility questionnaire. In general, patients must be 18 to 60 years of age and have failed all existing conventional treatments but be healthy enough to undergo a bone marrow transplant. A matched donor of bone marrow must be found from either a sibling or an unrelated person who has volunteered to donate marrow. Private insurance must cover the cost of the transplant and related medical expenses.

Crohns disease is usually discovered in adolescents and young adults but can occur from early childhood to older age. The incidence of Crohns disease varies in different parts of the world with rates of four to nine persons per 100,000 people in North America. According to the Crohns and Colitis Foundation of America, a leading advocacy organization, Crohns may affect more than 700,000 Americans. Of those affected by Crohns, about 10 percent suffer from the most severe form for which no treatment is completely effective.

Symptoms of Crohns may include pain, fever, diarrhea and weight loss. Substantial progress has been made in medical treatment of Crohns disease over the last 15 years. However, even with the best immunosuppressive therapy, less than half of patients with moderate to severe Crohns achieve long-term relief. When patients stop taking their medicines, their intestinal inflammation returns. Some severe infections have been seen in patients who took prolonged courses of medicines that suppress the immune system.

The burden of this disease lays heavily on those who dont respond to any therapy, McDonald said.

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New Clinical Trial Seeks to Cure Advanced Crohn's Disease by Replacing a Diseased Immune System with a Healthy One

2012-07-23 19:43

Tel Aviv - A clinical trial of ALS patients conducted by BrainStorm Cell Therapeutics shows its adult stem cell therapy is well-tolerated, appears to be safe and does not present undue risk, according to an interim safety review.

Moreover, in some patients signs of stabilisation of the disease were detected.

Israel-based BrainStorm is developing NurOwn for the treatment of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord.

"It's very uncommon to give at such an early point in a clinical study efficacy data, but we cannot ignore the fact on an individual basis we could see improvement in many of the patients involved, each one in different areas," Moshe Neuman, CEO of Biomedical Research Design, which serves as a contract research organisation for the trial, said.

In some patients breathing improved, in others it was muscle strength and in others it was speech, he told Reuters.

Neuman said a final report was expected by the end of the year after each patient has been observed for nine months.

BrainStorm President Chaim Lebovits said the preliminary results demonstrate that the stem cells have the potential not only to stop deterioration but perhaps even cure ALS.

"The coming phases in the trial will have to prove this, but these results also reaffirm our belief that we have an enormous potential of being successful with less severe indications such as multiple sclerosis and Parkinson's," he said.

Patients in the trial were transplanted with stem cells derived from their own bone marrow and treated with the NurOwn stem cell technology.

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Israel ALS stem cell trials hopeful

New cells to replace those destroyed in diabetes type 1, cells to help heal a heart attack, cells to cure leukemia this is the promise of stem cells. Some of this is happening now; more will be available in a few years. Stem cells will usher in the era of regenerative medicine, allowing the creation of cells, tissues and organs to treat or cure diseases and injuries. This will be a fundamental alteration in our approach to medical care and a transformational medical megatrend. And it will be very personalized medicine to provide the specific individual with custom tailored new cells and tissues for organ repair or replacement. Extensive use of stem cells as therapy is still in its infancy. Call it infancy because there is so much basic science still to be understood, that it will be quite some years before we will see stem cells being used on any sort of regular basis to treat diabetes, Parkinsons disease, or heart failure after a heart attack. But time flies, many investigators are hard at work and the science may advance quickly. There are exceptions; stem cells are being actively used for a few situations and have been for many years. Among them are bone marrow or stem cell transplantation for diseases like leukemia, some cancers being treated with very high doses of chemotherapy or some individuals, especially children, with immune disorders. Since stem cells have the potential to be of ever increasing importance to medical care, albeit not for a few years, it is important to understand just what a stem cell is, generally how the various types of stem cells differ from each other and how they are either found in the body or produced in the laboratory. The key characteristics of stem cells are that 1) they can replicate themselves and 2) they can become mature cells that make up the tissue and organs of the body. Embryonic stem cells are found in the earliest divisions of the fertilized ovum and can become any of the bodys approximately 200 types of cells (liver, lung, brain) and they have the capacity when placed in tissue culture in the laboratory to divide and to replicate themselves indefinitely. We call them pluripotent in that they can become any of the various types of cells in the body. Think of them as the most fundamental cellular building block that can create the tissues and organs of our body. Adult stem cells, as the name implies, can be found in the bodies of adults (or newborns and children for that matter.) They also can self replicate but when placed in tissue culture it has not been possible to have them replicate indefinitely as embryonic stem cells do. Adult stem cells generally only can differentiate into one type of the bodys cells or tissue, i.e., are unipotent. For example muscle stem cells only become muscle cells but not liver cells. But some adult stem cells, such as those from the bone marrow, can become multiple but not all types of cells. Stem cells obtained from the umbilical cord of a newborn baby are more like adult stem cells in that they can develop into some but apparently not all cells types. In effect, they are further along in the chain of differentiation.

There are also other types of stem cells that as of now are being produced in the laboratory and which have many of the attributes of embryonic stem cells nuclear transfer, induced pluripotent, and protein-induced pluripotent stem cells, among others. To create the nuclear transfer stem cell, an unfertilized egg is obtained from a womans ovary. The egg has its nucleus extracted by a micropipette and then has the nucleus of an adult cell inserted in its place. This nucleus might be obtained from a skin cell taken from the arm of a patient with a particular problem such as diabetes. The newly created cell is placed in culture and with the appropriate signals begins to act like an embryonic stem cell in that it will divide and replicate itself and with the appropriate signals the daughter cells can become various body cell types. The hope is that these cells, genetically identical to the patient who had the skin biopsy, could be grown up into a vast number of in this example pancreatic islet cells and used to treat this individual patients diabetes.

The induced pluripotent stem cell (or iPSC) also has many of the embryonic stem cells characteristics. It is produced by taking a persons cells such as from the skin of the arm and then stimulating them by inserting a few key genes, using a retrovirus. These genes reprogram the cell to revert to what is similar to an embryonic stem cell. The concern of course is that it is induced using a virus. More recent experiments have found that certain proteins can reprogram the cell just as can the virally-inserted genes. These stem cells are known as protein-induced pluripotent stem cells (piPSC). Both are being evaluated to determine if they can be as effective as embryonic stem cells. With each of these three techniques, a clear hoped for advantage is that a person can donate his or her own cells for transformation into stem cells and from there into whatever cell is of interest, such as pancreatic islet cells that secrete insulin. Such cells transplanted back into the person would be recognized as self and not trigger rejection with a graft vs. host response by the body. This concept with each technique is therefore all about personalized medicine.

Next time I will delve more deeply into adult stem cells followed the next time by embryonic stem cells. But in the meanwhile think of stem cell science as one more of those truly transformative medical megatrends that will revolutionize the practice of medicine in the years to come and in the process improve the healthcare of you and your family.

Link:
Medical Megatrends — Stem Cells — Part I of III

Today, I posted this to Twitter:

3 Innovative Cancer Treatments...But Which Is The Best Bet? seekingalpha.com/a/fjed $GSK $IMUC $VSTM #cancerSC via @seekingalpha — Jim Till (@jimtill) July 17, 2012

The article is about three companies that are working on treatments designed to target cancer stem cells (CSCs). The companies are OncoMed, Verastem and ImmunoCellular Therapeutics. The article is interesting.

Source:
http://cancerstemcellnews.blogspot.com/feeds/posts/default?alt=rss