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Washington, October 30 (ANI): Duke Medicine researchers have engineered cartilage from induced pluripotent stem cells that were successfully grown and sorted for use in tissue repair and studies into cartilage injury and osteoarthritis.

The finding suggests that induced pluripotent stem cells, or iPSCs, may be a viable source of patient-specific articular cartilage tissue.

"This technique of creating induced pluripotent stem cells - an achievement honoured with this year's Nobel Prize in medicine for Shimya Yamanaka of Kyoto University - is a way to take adult stem cells and convert them so they have the properties of embryonic stem cells," said Farshid Guilak, PhD, Laszlo Ormandy Professor of Orthopaedic Surgery at Duke and senior author of the study.

"Adult stems cells are limited in what they can do, and embryonic stem cells have ethical issues. What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue - in this case cartilage, which has no ability to regenerate by itself," Guilak noted.

Articular cartilage is the shock absorber tissue in joints that makes it possible to walk, climb stairs, jump and perform daily activities without pain. But ordinary wear-and-tear or an injury can diminish its effectiveness and progress to osteoarthritis.

Because articular cartilage has a poor capacity for repair, damage and osteoarthritis are leading causes of impairment in older people and often requires joint replacement.

In their study, the Duke researchers, led by Brian O. Diekman, PhD., a post-doctoral associate in orthopaedic surgery, aimed to apply recent technologies that have made iPSCs a promising alternative to other tissue engineering techniques, which use adult stem cells derived from the bone marrow or fat tissue.

One challenge the researchers sought to overcome was developing a uniformly differentiated population of chondrocytes, cells that produce collagen and maintain cartilage, while culling other types of cells that the powerful iPSCs could form.

To achieve that, the researchers induced chondrocyte differentiation in iPSCs derived from adult mouse fibroblasts by treating cultures with a growth medium. They also tailored the cells to express green fluorescent protein only when the cells successfully became chondrocytes. As the iPSCs differentiated, the chondrocyte cells that glowed with the green fluorescent protein were easily identified and sorted from the undesired cells.

The tailored cells also produced greater amounts of cartilage components, including collagen, and showed the characteristic stiffness of native cartilage, suggesting they would work well repairing cartilage defects in the body.

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Cartilage grown in lab dishes using stem cells

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

Verastem, Inc., (VSTM) a clinical-stage biopharmaceutical company focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, announced the presentation of data at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics on November 6-9, 2012, in Dublin, Ireland.

The details of the Verastem poster presentations are as follows:

Title: FAK Inhibitor VS-4718 Attenuates Breast Cancer Stem Cell Function and Inhibits Tumor Growth in Vivo Date: November 8, 2012, from 12:00 to 2:15 pm GMT Session: Signal Transduction Modulators Abstract Number: 400 Location: Auditorium at the Convention Centre Dublin

Title: The Pan-PI3K/mTOR Kinase Inhibitor VS-5584 Preferentially Targets Cancer Stem Cells in Breast Cancer Models Date: November 8, 2012, from 12:00 to 2:15 pm GMT Session: Signal Transduction Modulators Abstract Number: 405 Location: Auditorium at the Convention Centre Dublin

About Verastem, Inc. Verastem, Inc. (VSTM) is a clinical-stage biopharmaceutical company focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells. Cancer stem cells are an underlying cause of tumor recurrence and metastasis. Verastem is developing small molecule inhibitors of signaling pathways that are critical to cancer stem cell survival and proliferation: FAK, PI3K/mTOR and Wnt. For more information, please visit http://www.verastem.com.

Forward-looking statements: Any statements in this press release about future expectations, plans and prospects for the Company constitute forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements. The Company anticipates that subsequent events and developments will cause the Companys views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.

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Verastem to Present at the 2012 Symposium on Molecular Targets and Cancer Therapeutics

Researchers have created adult cartilage from stem cells found in mice. The discovery could lead to new treatments for osteoarthritis and cartilage injury.

The finding is especially important because cartilage does not regenerate itself.

Experts at Duke University created the cartilage from adult cells that have been genetically altered to be structurally similar to embryonic stem cells. The technique of developing those cells, known as induced pluripotent stem cells iIPSCs), was originated by Shimya Yamanaka of Kyoto University. It won this years Nobel Prize for medicine.

The Duke researchers built on that technique to create the cartilage.

What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue, senior author Farshid Guilak said in a news release. iPSCs can be used to make high quality cartilage, either for replacement tissue or as a way to study disease and potential treatment.

Further studies, this time on humans, are needed, he said.

The findings were published in the Proceedings of the National Academy of Sciences.

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Breakthrough: Cartilage Developed from Cells

MONDAY, Oct. 29 (HealthDay News) -- Scientists who created cartilage from adult stem cells in mice say their success could lead to new treatments for cartilage injury and osteoarthritis.

The cartilage was created using induced pluripotent stem cells, which are adult cells that have been genetically altered to have the characteristics of embryonic stem cells. Induced pluripotent stem cells (iPSCs) have the potential to become different types of specialized cells.

"What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue -- in this case cartilage, which has no ability to regenerate by itself," study senior author Farshid Guilak, a professor of orthopedic surgery at Duke University in Durham, N.C., said in a university news release.

The study was published online Oct. 29 in the journal Proceedings of the National Academy of Sciences.

Study leader Brian Diekman, a post-doctoral associate in orthopedic surgery, said the multi-step process used by the researchers shows "that iPSCs can be used to make high-quality cartilage, either for replacement tissue or as a way to study disease and potential treatments."

Guilak added that the advantage of this technique is "we can grow a continuous supply of cartilage in a dish." He said that in addition to cell-based therapies, this technology can also provide "patient-specific cell and tissue models that could be used to screen for drugs to treat osteoarthritis, which right now does not have a cure or an effective therapy to inhibit cartilage loss."

However, results achieved in animal trials do not necessarily apply to humans. The researchers said they next plan to use human induced pluripotent stem cells to test the cartilage-growing technique.

-- Robert Preidt

Copyright 2012 HealthDay. All rights reserved.

SOURCE: Duke University, news release, Oct. 29, 2012

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Stem Cells to Cartilage? Promising Results Seen in Mice

Public release date: 31-Oct-2012 [ | E-mail | Share ]

Contact: Sarah Collins sarah.collins@enterprise.cam.ac.uk 44-012-237-60335 Cambridge Enteprise University of Cambridge

The potential therapeutic applications of stem cells such as regenerating damaged tissues or organs have generated a great deal of interest over the past decade. While these types of applications are exciting, it is a long journey from lab to clinic. The most immediate impact of stem cells on human health will most likely come from their use in the development of new drugs.

The ability to generate stem cells by reprogramming cells from patients' skin has revolutionised human stem cell research. These cells, known as human induced pluripotent stem cells (hIPSC), can be differentiated into almost any cell type, allowing the opportunity to have a ready source of human cells for testing new therapies. DefiniGEN, a new spin-out company from the University of Cambridge, has been formed to supply hIPSC-derived cells to the drug discovery and regenerative medicine sectors. The company is based on the research of Dr Ludovic Vallier, Dr Tamir Rashid and Professor Roger Pedersen of the Anne McLaren Laboratory of Regenerative Medicine.

Dr Vallier led a team, including Dr Rashid, Dr Nick Hannan and Candy Cho, that developed the technology to generate human liver cells (hepatocytes) in a highly reproducible and scalable manner for commercial use. This represents a major breakthrough in the costly and time-consuming process of developing new therapies. The technology has also been used to effectively model a diverse range of inherited liver diseases and has the potential to accelerate the development of new therapies for these conditions.

The liver is the key organ for metabolising drugs and removing toxins from the body. Consequently, it is often affected by toxic compounds. Demonstrating that a new drug candidate is free from liver toxicity is a key test in the development process, and it is a test that most drug candidates fail.

"If a drug's failure occurs in the clinical phase of development, a great deal of time and money will have been lost," said Dr Vallier. "Therefore, identifying toxic drugs as early as possible is vital to the safety and efficiency of the drug discovery process."

Currently, either primary human hepatocytes or immortalised cell lines are used for toxicity testing. Primary hepatocytes have a high degree of batch-to-batch variation, are expensive and difficult to obtain in suitable quantities, while immortalised cell lines are an inferior model for toxicity testing.

The hIPSC-derived cells produced by DefiniGEN, however, show many of the functional characteristics of primary cells, are highly reproducible and can be made in large quantities, making them ideal for toxicity testing.

In addition, the company's OptiDIFF platform has produced libraries of disease-modelled cells for a range of diseases, including the most common inherited metabolic conditions such as Familial hypercholesterolemia and Alpha 1 anti-trypsin disorder. The cells effectively demonstrate key pathologies of diseases and can be used to improve lead optimisation studies, assisting the development of new therapies for these conditions. The company will also develop pancreatic beta cell products which, in combination with hepatocyte products, will enable the optimised development of new therapeutics for diabetes.

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The role of stem cells in developing new drugs

The Food and Drug Administration has informed the Sugar Land company involved in Gov. Rick Perry's adult stem-cell procedure that it is illegally marketing an unlicensed drug.

In a warning letter, the FDA gave Celltex Therapeutics Corp. 15 business days to submit a plan to address the agency's concerns, including correcting previously cited manufacturing problems. The letter said that failure to respond promptly could result in seizure or injunction by the FDA.

"Based on (our) information, your product violates the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act," says the letter, sent on Sept. 24 and publicly posted Tuesday.

The letter comes about six months after the FDA made a 10-day inspection of the facilities where Celltex banks and grows stem cells taken from prospective patients. The agency subsequently filed a report, obtained by the Chronicle in June, detailing dozens of manufacturing deficiencies, from incorrectly labeled products to failed sterility tests.

The new warning letter reiterates those problems and asks for more information about them.

David Eller, Celltex's CEO, was unavailable Tuesday, but a public relations official said the company on Wednesday would make available a redacted copy of its letter to the FDA.

In a previous news release, Eller said Celltex "respectfully but firmly" disagreed with the FDA's position that its process causes the cells to be considered biological drugs and thus subject to the federal agency's regulations. Biological drugs involve living human cells, as opposed to chemically synthesized drugs.

"We are considering all options as we work with the agency toward a resolution," Eller said in the release.

Adult stem cells multiply to replenish dying cells. Long used to treat leukemia and other cancers, they have recently shown promise for tissue repair in other diseases, though most scientists in the field consider them not ready for mainstream use.

Treatment, at a price

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FDA issues warning letter to local stem cell company

The nuclei of brain stem cells in some Parkinson's patients become misshapen with age. The discovery opens up new ways to target the disease.

Nubby nucleus: Brain cells from a deceased Parkinsons patient have deformed nuclei (bottom) compared with normal brain cells from an individual of a similar age. Merce Marti and Juan Carlos Izpisua Belmonte

Stem cells in the brains of some Parkinson's patients are increasingly damaged as they age, an effect that eventually diminishes their ability to replicate and differentiate into mature cell types. Researchers studied neural stem cells created from patients' own skin cells to identify the defects. The findings offer a new focus for therapeutics that target the cellular change.

The report, published today in Nature, takes advantage of the ability to model diseases in cell culture by turning patient's own cells first into so-called induced pluripotent stem cells and then into disease-relevant cell typesin this case, neural stem cells. The basis of these techniques was recognized with a Nobel Prize in medicine last week.

The authors studied cells taken from patients with a heritable form of Parkinson's that stems from mutations in a gene. After growing several generation of neural stem cells derived from patients with that mutation, they saw the cell nuclei start to develop abnormal shapes. Those abnormalities compromise the survival of the neural stem cells, says study coauthor Ignacio Sancho-Martinez of the Salk Institute for Biological Studies in La Jolla, California.

Today's study "brings to light a new avenue for trying to figure out the mechanism of Parkinson's," says Scott Noggle of the New York Stem Cell Foundation. It also provides a new set of therapeutic targets: "Drugs that target or modify the activity [of the gene] could be applicable to Parkinson's patients. This gives you a handle on what to start designing drug screens around."

The strange nuclei were also seen in patients who did not have a known genetic basis for Parkinson's disease. The authors suggest this indicates that dysfunctional neural stem cells could contribute to Parkinson's. While that conclusion is "highly speculative," says Ole Isacson, a neuroscientist at Harvard Medical School, the study demonstrates the "wealth of data and information that we now can gain from iPS cells."

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Parkinson's cells

The nuclei of brain stem cells in some Parkinson's patients become misshapen with age. The discovery opens up new ways to target the disease.

Nubby nucleus: Brain cells from a deceased Parkinsons patient have deformed nuclei (bottom) compared with normal brain cells from an individual of a similar age. Merce Marti and Juan Carlos Izpisua Belmonte

Stem cells in the brains of some Parkinson's patients are increasingly damaged as they age, an effect that eventually diminishes their ability to replicate and differentiate into mature cell types. Researchers studied neural stem cells created from patients' own skin cells to identify the defects. The findings offer a new focus for therapeutics that target the cellular change.

The report, published today in Nature, takes advantage of the ability to model diseases in cell culture by turning patient's own cells first into so-called induced pluripotent stem cells and then into disease-relevant cell typesin this case, neural stem cells. The basis of these techniques was recognized with a Nobel Prize in medicine last week.

The authors studied cells taken from patients with a heritable form of Parkinson's that stems from mutations in a gene. After growing several generation of neural stem cells derived from patients with that mutation, they saw the cell nuclei start to develop abnormal shapes. Those abnormalities compromise the survival of the neural stem cells, says study coauthor Ignacio Sancho-Martinez of the Salk Institute for Biological Studies in La Jolla, California.

Today's study "brings to light a new avenue for trying to figure out the mechanism of Parkinson's," says Scott Noggle of the New York Stem Cell Foundation. It also provides a new set of therapeutic targets: "Drugs that target or modify the activity [of the gene] could be applicable to Parkinson's patients. This gives you a handle on what to start designing drug screens around."

The strange nuclei were also seen in patients who did not have a known genetic basis for Parkinson's disease. The authors suggest this indicates that dysfunctional neural stem cells could contribute to Parkinson's. While that conclusion is "highly speculative," says Ole Isacson, a neuroscientist at Harvard Medical School, the study demonstrates the "wealth of data and information that we now can gain from iPS cells."

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Stem Cells Reveal Defect in Parkinson's Cells

Public release date: 17-Oct-2012 [ | E-mail | Share ]

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

SEATTLE One of the world's leading bone marrow transplant experts is recommending a significant change to current transplant practice for patients who need marrow or adult stem cells from an unrelated donor to treat hematologic malignancies. Fred Appelbaum, M.D., director of the Clinical Research Division at Fred Hutchinson Cancer Research Center, asserts that bone marrow not circulating, peripheral blood, which is the current norm should be the source for unrelated donor adult stem cells for most patients who require a transplant. The reason: because there is less incidence of chronic graft-versus-host disease (GVHD), which can be a debilitating side effect of transplantation.

Appelbaum called for the change in an Oct. 18 editorial in The New England Journal of Medicine in response to a new study, published in the same issue, which compared survival rates and side effects of treating patients with hematopoietic adult stem cells derived from bone marrow versus circulating peripheral blood. The study found a higher incidence of chronic GVHD 53 percent when peripheral blood was the source of stem cells for transplant versus 41 percent when bone marrow is the source.

"For the majority of unrelated transplants following a standard high-dose preparative regimen, bone marrow should be used since survival is equivalent with the two sources but the incidence of chronic graft-versus-host disease, which can be a debilitating complication, is significantly less with marrow," Appelbaum wrote.

GVHD is a common side effect in people who receive cells from an unrelated donor. It occurs when the transplanted cells recognize the recipient's tissues as foreign and attack the tissues. This can cause a variety of problems, including skin rashes, liver problems and diarrhea. Chronic GVHD can develop any time between three months and three years after the transplant and can range from mild to serious in intensity.

Appelbaum said that stem cells derived from peripheral blood should only be used for the minority of patients in whom the benefits outweigh the risks. These include patients in need of rapid engraftment, such as those with life-threatening infections, or patients at high risk for graft rejection, such as those who receive reduced-intensity conditioning that does not include intensive chemotherapy.

For the past 10 years peripheral blood has been the norm as a source of matched related and matched unrelated adult stem cells for transplant because, despite the higher risk of GVHD, they are easier to harvest from the donor, they can be stimulated to grow in large numbers prior to harvesting, and they engraft, or set up shop, quickly inside the recipient's body.

The potential impact if such a practice change were widely implemented is large. Currently, about 75 percent of unrelated donor transplants are done using stem cells that are collected from the peripheral blood of donors. About 70 percent of all patients who undergo a life-saving transplant to treat blood cancers such as leukemia require an unrelated donor. Collecting adult stem cells from bone marrow is a more invasive process than collecting them from the bloodstream.

According to Appelbaum, about 5,500 unrelated donor transplants were performed in the United States last year. More than 20 million potential unrelated donors are typed and listed in registries in the Americas, Europe and Asia.

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Leading bone marrow transplant expert recommends significant change to current practice

Public release date: 16-Oct-2012 [ | E-mail | Share ]

Contact: Bryan Ghosh bghosh@plos.org 44-122-344-2837 Public Library of Science

Researchers at the University of Helsinki believe they have discovered stem cells that play a decisive role in the growth of new blood vessels. If researchers learn to isolate and efficiently produce these stem cells found in blood vessel walls, the cells could offer new opportunities for developing therapeutics to treat diseases, such as cardiovascular disease and cancer. The study reporting the discovery of these stem cells is published in the open access journal PLOS Biology on October 16.

The growth of new blood vessels, known as neoangiogenesis, occurs during the repair of damaged tissue and organs in adults. However, malignant tumours also grow new blood vessels in order to receive oxygen and nutrients. As such, neoangiogenesis is both beneficial and detrimental to health, depending on the context, requiring therapeutic approaches that can either help to stimulate or prevent it. Therapeutics that aim to prevent the growth of new blood vessels are already in use, but the results are often more modest than predicted.

Adjunct Professor Petri Salvn and his team, from the University of Helsinki, now report that these stem cells can be found among the cellsso-called endothelial cellsthat line the inside of blood vessel walls. He explains, "we succeeded in isolating endothelial cells with a high rate of division in the blood vessel walls of mice. We found these same cells in human blood vessels and blood vessels growing in malignant tumours in humans. These cells are known as vascular endothelial stem cells, abbreviated as VESC. In a cell culture, one such cell is capable of producing tens of millions of new blood vessel wall cells".

From their studies in mice, the team are able to show that the growth of new blood vessels weakens, and the growth of malignant tumours slows, if the amount of these cells is below normal. Conversely, new blood vessels form where these stem cells are implanted.

"The identification and isolation of an entirely new adult stem cell type is a significant discovery in stem cell biology." explains Salvn. "Endothelial stem cells in blood vessels are particularly interesting, because they offer great potential for applications in practical medicine and the treatment of patients."

If an efficient method of vascular endothelial stem cell production could be developed, it could offer new treatment opportunities in situations where damaged tissue or diseases call for new blood vessel growth, or where the constriction or dysfunction of blood vessels deprives tissues of oxygen, for example in cardiac disease. These cells also offer new opportunities for developing therapeutics that seek to prevent new blood vessel growth in malignant tumours.

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Funding: The work was supported by the Finnish Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish,or preparation of the manuscript.

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Researchers discover new blood vessel-generating cell with therapeutic potential