Archive for the ‘Stem Cell Research’ Category

First Clinical Trial of Autologous Cardiac Stem Cells Shows Positive Results

Last Updated on Tuesday, 22 November 2011 03:13 Written by admin Tuesday, 22 November 2011 03:13

Initial data from the first ever trial to evaluate autologous cardiac stem cell (CSC) transplants in humans suggests that the treatment improves left ventricular (LV) systolic function by an average of 12% over one year, and reduces infarct size in patients with severe heart failure due to ischemic heart disease. The trial investigators say the results triple the 4% average improvement that they had projected and calls for the start of larger Phase II trials.

Stage A of the ongoing open-label Phase I SCIPIO (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy) study, by investigators at the University of Louisville and Brigham and Women’s Hospital, is evaluating CSC transplantation in patients with severe heart failure secondary to ischemic cardiomyopathy. The target population includes patients who underwent coronary artery bypass grafting (CABG), had LV ejection fraction (EF) of less than or equal to 40%, and a previous myocardial infarction.

Treated patients were administered with about a million autologous CSCs by intracoronary infusion, at a mean of 113 days after CABG. To generate the cardiac stem cells, tissue from the right atrial appendage was harvested from the patients at the time of CABG, and CSCs were isolated and expanded at the Brigham and Women’s Hospital.

Data from 14 of 16 patients assigned to the treatment group, and seven from the control group (best supportive care), have now been published in The Lancet to coincide with data presentation at the American Heart Association’s Scientific Sessions meeting in Orlando, FL. The reported data showed that autologous CSC transplantation led to an increase in LVEF from 30.3% before CSC infusion to 38.5% at four months after infusion. In contrast, the LVEF of seven control patients didn’t change over eight months. The benefits of CSC transplantation was even more pronounced at one year in eight evaluated patients, for whom LVEF increased by 12.3 ejection fraction units compared with baseline. In the seven treated patients evaluated using MRI, infarct size was also shown to have decreased by 24% at 4 months, and 30% at one year.

The trial has been led by Roberto Bolli, M.D., at the University of Louisville and Piero Anversa, Ph.D., at Brigham and Women’s Hospital/Harvard Medical School in Boston. “The results are striking,” Dr. Bolli states. “While we do not yet know why the improvement occurs, we have no doubt now that ejection fraction increased and scarring decreased. If these results hold up in future studies, I believe this could be the biggest revolution in cardiovascular medicine in my lifetime.”

The published paper in The Lancet is titled “Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised Phase I trial.”

Source: http://www.genengnews.com/gen-news-highlights/first-clinical-trial-of-autologous-cardiac-stem-cells-shows-positive-results/81245949/

Posted under Cell Analysis, Discoveries, Innovations and Patents, Genetics & Pharmacogenetics, New Drugs, R & D, Reports, Research Projects, Stem Cell Research | Comments Off

Scientists Use Mutant Protein to Inhibit Cancer Stem Cells and Resensitize Tumors to Lapatinib

Last Updated on Wednesday, 14 September 2011 01:56 Written by admin Wednesday, 14 September 2011 01:56

Blocking a cancer cell protein from binding to three other proteins may provide a new approach to cancer therapy that both reduces populations of breast cancer initiating cells (BCICs) in breast tumors and sensitizes the tumors to existing treatments such as lapatinib or paclitaxel, scientists claim. The technique uses a specially designed lipid-based vector to make cancer cells, including BCICs, express a mutant form of the BH3-only proapoptotic protein (Bik).

The mutant protein, called BikDD, essentially competes with Bik for binding to the three antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1. This results in significant antitumor and apoptotic effects and, importantly, improves the anticancer effects of lapatinib or paclitaxel in relevant tumor types, claim the University of Texas M.D. Anderson Cancer Center researchers.

Reporting on their in vitro and in vivo studies in Cancer Cell, Mien-Chie Hung, Ph.D., and colleagues, claim that their results in addition highlight an important role for the antiapoptotic Bcl-2 proteins in the survival of BCICs. Their paper is titled “BikDD Eliminates Breast Cancer Initiating Cells and Synergizes with Lapatinib for Breast Cancer Treatment.”

There are currently no drugs that can effectively reduce BCICs in patients, and resistance of these cells to chemo- and radiotherapies means that following therapy, the relative proportions of these cells in the tumors increase, and eventually lead to relapse, the researchers report.

One of the key mechanisms accounting for chemoresistance in cancer-initiating cells is their low susceptibility to apoptosis, and previous lines of research have implicated the Bcl-2 family of proteins in the ability of cancer cells to escape apoptosis in response to cancer therapy. For example, studies have shown that overexpression of the antiapoptosis proteins Bcl-2, Bcl-xL, and Mcl-1 correlates with high tumor grade, poor patient prognosis, and the development of resistance to chemotherapy.

More specifically, the acquired resistance of breast cancer cells to lapatinib has been linked with overexpression of Bcl-2 and Mcl-1, suggesting that lapatinib-induced apoptosis requires inactivation of antiapoptotic Bcl-2 family proteins.

The Anderson team hypothesized that because the overall expression pattern of Bcl-2, Bcl-xL, and Mcl-1 appears to correlate inversely with apoptotic response following drug treatment, an antagonist that targets all of these antiapoptotic proteins might stand a good chance of acting to reinstate apoptotic pathways in breast cancer cells.

The researchers’ approach to achieving this involved introducing into cancer cells a competitive inhibitor, a mutant form of the Bik protein that normally binds to to Bcl-2, Bcl-xL, and Mcl-1. To test whether this approach might work, they delivered a lentivirus carrying the BIKDD gene into cells from the human breast cancer line MDA-MB-468. These tests provided confirmation that expression of BikDD significantly inhibited cell growth and resulted in large numbers of apoptotic bodies.

Interestingly, expression of BikDD also reduced the population of CD44⁺/CD24^-cells (which have previously been identified as breast cancer stem-type cells) and reduced mamosphere formation in vitro. These results were recapitulated in a different cell line: Infecting BT474 human breast cancer cells with the BikDD vector also led to a reduction in the CD44⁺/CD24^-population and of mammosphere formation. Importantly, introducing BikDD into human primary breast tumor samples that had undergone radiation therapy similarly led to significant reductions in the CD44⁺/CD24^-cell population, and mammosphere formation. Equivalent results were obtained using primary mouse tumor cells: administration of BikDD led to marked reductions in populations of mouse breast stem cells, and again blocked mammosphere formation.

The team went on to investigate whether BikDD could also inhibit cancer initiation. They infected mamospheres from MDA-MB-468 parental cells using the BikDD vector, and then injected surviving cells into NOD/SCID mice. Compared with untreated MDA-MB-468 cells, which readily formed tumors, the BikDD-infected cells demonstrated much lower cancer-forming capacity in vivo, and virtually no tumors developed in the recipient animals, suggesting that BikDD treatment reduced the BCIC population, the researchers remark.

They then adopted a gene therapy protocol that allows for the assay of cancer initiation activity in tumor xenografts growing in mice after BikDD treatment. This approach exploits a cancer cell-targeting platform developed at the MD Anderson Center, called VISA, VISA’ (VP16-GAL4-WPRE integrated systemic amplifier), which is based on an engineered, promotor-driven expression vector designed to enhance cancer-specific promoter activity by several hundred-fold, and prolong duration of gene expression without loss of cancer specificity.

Mice bearing MDA-MB-468 tumor xenografts were treated using either a control vector-liposome or with VISA-claudin4-BikDD-liposome complexes, and resulting tumor tissues removed and subsequently passaged into new animals. The results showed that transplanted cells taken from mice that had been treated with VISAclaudin4-BikDD-liposome complexes were far less tumorigenic in new animals than those from mice treated with vector-control-liposome complexes. In fact, none of the animals given tumor cells from the VISA-claudin4-BikDD-treated mice developed cancers. These animals also demonstrated lower numbers of CD44+/CD24^- cells, and fewer mammospheres formed after VISAclaudin4-BikDD treatment.

Because the team’s previous work had suggested that in comparison with wild-type Bik, BikDD demonstrates enhanced binding affinity to Bcl-2 antiapoptotic proteins, they looked more specifically at the effect of its major binding partners Bcl-2, Bcl-xL, and Mcl-1, in BCICs. Using combinations of shRNAs to silence the three Bcl-2, Bcl-xL, and Mcl-1 either individually or in combinations in cultured cells, the researchers found that while knocking down any of the proteins individually had no effect on the numbers of BCIC cells, silencing all three simultaneously reduced the CD44⁺/CD24^-population to 25% of that in control MDA-MB-468 cells, and consequently decreased mammosphere formation. Similar results were obtained using different shRNAs (to verify that the effects weren’t due to off-target activity), and in a different cell line.

“Taken together, we determined that efficient induction of apoptosis in BCICs requires silencing of all three antiapoptotic Bcl-2 proteins, which suggests that co-antagonism of multiple Bcl-2 antiapoptotic proteins by BikDD may have a better killing effect against BCICs than targeting individual antiapoptotic proteins, which is likely due to their functional redundancy in the survival of BCICs,” the authors state.

They then exploited the cancer cell-targeting VISA technology to test the therapeutic effects of BikDD gene therapy both in vitro and in vivo. To this end, they engineered a VISA vector that would express BikDD under the claudin-4 promoter that is selectively expressed in breast cancer cells. Testing the resulting VISA-claudin4–BikDD vector in a panel of breast cancer and normal cell lines confirmed that it strongly inhibited the growth of different breast cancer cell lines, but had little or no effect on the growth of normal human cells. The tumor inhibitory effects of the vector were subsequently confirmed in vivo, in one syngeneic mouse breast tumor and multiple human breast tumor orthotopic xenograft models.

Prior studies had demonstrated that the clinical efficacy of anti-Her2 drugs such as lapatinib and trastuzumab are greatly limited by either inoperative apoptosis machinery or overexpression of Bcl-2 antiapoptotic proteins, the researchers add. With this in mind they moved on to examine whether either the administration of BikDD, or the inhibition of antiapoptotic Bcl-2 proteins could enhance the therapeutic effect of lapatinib in breast cancer cells. They found that VISA-claudin4-BikDD effectively sensitized BT474 and MDA-MB-453 (Her2⁺), and MDA-MB-468 and BT20 (EGFR⁺) cells to lapatinib. Similarly, inhibiting Bcl-2, Bcl-xL, and Mcl-1 using shRNAs also sensitized EGFR⁺/Her2⁺ breast cancer cells to lapatinib, to about the same degree as BikDD vector therapy. Significantly, VISA-claudin4-BikDD therapy in addition sensitized multiple breast cancer cell lines to paclitaxel in vitro.

To further examine the therapeutic efficacy of VISA-claudin4-BikDD plus lapatinib combination in vivo, the researchers then treated mice bearing Her2⁺ BT474 human breast cancer xenografts, with VISA-claudin4-BikDD and/or lapatinib. While VISA-claudin4-BikDD or lapatinib alone had significant tumor inhibitory effects, combining the two treatments demonstrated even better therapeutic efficacy. These results were confirmed in mice carrying tumors derived from different breast cancer cell lines.

To evaluate therapy on BCIC cells in vivo, VISA-claudin4-BikDD, lapatinib, or paclitaxel were either alone or in combination, to treat a MDA-MB-468 tumor orthotopic xenograft mouse model. Consistent with the in vitro data, BikDD treatment significantly reduced the percentage of CD44⁺/CD24^- cells, whereas, as expected, paclitaxel therapy on its own increased this population by about threefold. In fact, combining the two treatments was better at suppressing tumor growth than VISA-claudin3-BikDD therapy alone, even after therapy was withdrawn, the authors note. Similar results were observed as a result of combination therapy with VISAclaudin4-BikDD and lapatinib.

Collectively, these results indicate that BikDD driven by VISA-claudin4 vector potently reduced the CD44⁺/CD24^- population in vivo even after chemotherapy, and efficiently attenuated tumor growth after cessation of drug treatment, suggesting that VISA-claudin4-BikDD treatment may serve as a potential therapeutic approach to kill BCICs, which is considered as a major barrier for breast cancer treatment,” the authors write. “By using our newly developed VISA-claudin4-BikDD for treating breast cancer, it is likely that therapeutic efficacy will be enhanced and potential side effects prevented as we have shown that BikDD targets both non-BCICs and BCICs and demonstrates virtually no toxicity in normal cells…Therefore, it is worthy of moving VISA-claudin4-BikDD into a clinical trial.”

Source: http://www.genengnews.com/gen-news-highlights/scientists-use-mutant-protein-to-inhibit-cancer-stem-cells-and-resensitize-tumors-to-lapatinib/81245670/

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Scientists Claim Differentiated Cancer Cells Can Convert to Stem-Like Cells to Maintain Equilibrium

Last Updated on Friday, 19 August 2011 04:42 Written by admin Friday, 19 August 2011 04:42

Cells in individual tumors can interconvert into different cell types including reverting into cancer stem cells in order to maintain equilibria in terms of the proportion of cells existing in different states within the cancer, researchers claim.They found that rather than existing as a hierarchical society in which all cells are derived from cancer stem cells, cancers exist as a decentralized society of different cell types that can sense when one type of cell has been depleted and generate new cells of the relevant type to take their place.

The group included scientists at the Massachusetts of Institute of Technology Broad Institute, Tufts University, and Harvard Medical School. Details are published in Cell in a paper titled “Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells.” Results could have significant implications for cancer cell therapy, claim lead researchers Eric S. Lander, Ph.D., and Piyush B. Gupta, Ph.D., because removing cancer stem cells will just prompt other cell types in the tumor to convert into stem cells to top up the population.

One of the puzzling features of cancer cell populations is their ability to retain phenotypic equilibrium over extended periods of time, the team writes. Populations of cancer cells often harbor subpopulations with specific cell-surface marker profiles, which are stably maintained across many cell divisions in culture.

To investigate the basis of this equilibrium-maintaining phenomenon further, the researchers isolated and separately cultured three cell types—stem-like, basal, and luminal—from two different human breast cancer lines derived from primary tumors. Each of the three cell types was confirmed to display specific morphological and cell surface marker characteristics.

These relatively pure subpopulations of cells, which each represented a given differentiation state, were then allowed to expand in culture, and relevant population dynamics monitored over time. Surprising, the researchers found that when they assessed the relative proportions of stem-like, basal, and luminal cells in each originally ‘pure’ population after expansion, there had been an evident rapid progression back to equilibrium proportions.

Two lines of evidence indicated that this progression was due to interconversion between states, rather than as a result of differential growth rates of cells in the basal, stem-like, or luminal states, they claim. Firstly, there was no difference in the proliferation rates of the stem-like, basal, or luminal subpopulations sorted from either of the two stem cell lines: they all replicated at about the same rate.

Secondly, given the purity of the original sorted populations and the rapid rate of return to equilibrium proportions, some minority subpopulations would need to have been dividing at more than three times per day to achieve the observed proportions through differential growth rate alone. “Such a high proliferation rate is implausible because even the most rapidly dividing human cells— embryonic stem cells—require at least 24 hours to complete a proliferation cycle,” they claim.

Based on the notion that interconversion between cell states was therefore occurring, the team used data from their expanded breast cancer cell populations to developed a Markov model, in which the cell type transition probabilities depend only on a cell’s current state, not on its prior state. The inferred Markov transition probabilities thus make it possible to quantitatively predict how a population of cells evolves over time, given the initial proportions of cells in different states.

The resulting model made several predictions about how the cell populations would develop, and these were confirmed in the cultured breast cancer populations, the researchers note. However, a number of unexpected predictions also emerged. One of these was that basal and luminal cells can transition back into a stem-like state: “that is, cancer stem-like cells can arise from non-stem-like cells.” This essentially contradicts current concepts relating to normal tissues, which assume a rigid lineage-hierarchy in which stem cells can give rise to nonstem cells, but not vice versa, they write.

They tested this particular prediction by implanting either freshly sorted, or sorted and then cultured subpopulations of tumor cells in mice. As expected according to traditional dogma, only the stem-like fraction could efficiently seed tumors, and neither the luminal nor basal fraction was capable of doing so.

However, because the lack of tumor-seeding ability displayed by the basal and luminals could have been due to their inability to survive after transplantation, the researchers repeated the exercise by co-inoculating the cells with GFP-labeled, irradiated parental carrier cells from one of the breast cancer lines. Under these conditions, all three fractions (stem-like, basal, and luminal) were equally capable of efficiently seeding tumors.

Moreover, examination of the tumors arising from basal and luminal subpopulations mixed with irradiated carrier cells revealed the presence of significant numbers of stem-like cells. The proportions of basal, stem-like, and luminal cells contained in the resulting tumors were comparable irrespective of the sorted subpopulation initially used to seed the tumor.

“Collectively, these results demonstrated that the luminal and basal fractions can indeed regenerate functional stem-like cells in vivo and suggested that convergence toward equilibrium cell-state proportions could be occurring due to cell-state interconversion within tumors,” the authors write. “A specific prediction of this quantitative model is that any subpopulation of cancer cells will return to a fixed equilibrium of cell-state proportions over time, provided that it is possible through one or more interconversions to transition between any two states.”

The de novo generation of cancer stem cells has implications for the effectiveness of anticancer therapies focused on killing this cell type, because of the ability of other cancer cell types to regenerate cancer stem cells after cessation of therapy and lead to renewed tumor growth, they add. “Therefore, in order to be effective, cancer therapies will need to combine agents that are selectively toxic to cancer stem cells with agents that either target the bulk noncancer stem cell populations within tumors or inhibit transitions from noncancer stem cell to cancer stem cell states.”

The team claims their model could also be extended to other biological settings in which stochastic state transitions occur, either in normal or diseased contexts.

Source: http://www.genengnews.com/gen-news-highlights/scientists-claim-differentiated-cancer-cells-can-convert-to-stem-like-cells-to-maintain-equilibrium/81245572/

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Stem cell research and use in veterinary medicine

Last Updated on Thursday, 7 July 2011 01:09 Written by admin Thursday, 7 July 2011 01:09

Stem cells show so much promise in human medicine. Cells that have the ability to become anything that the body needs is nothing short of a miracle. What is the role of stem cells in veterinary medicine? Do stem cells have a place? Many say they very much do.

Stem cells are able to be harvested from animals and are primarily used in horses, dogs, and cats for arthritic conditions.

There is much less controversy in veterinary medicine over the use of stem cells (at least at the present time) because of where they are harvested, or obtained. Rather than take stem cells from an umbilical cord or from an unborn fetus, the cells are harvested from the host itself.

How is this possible? Right now we know there is a certain amount of stem cells that exists in adult animals in either fat or bone marrow. These stem cells are considered adult stem cells and are somewhat limited in there ability to become “any cell” as compared to embryonic stem cells. However, adult stem cells can become cells similar to themselves.

What does this mean? There are individual reports of stem cells being used in veterinary medicine for conditions like ligament and tendon injuries in horses, as well as to treat a condition called laminitis. Everyone knows what tendons and ligaments are but what is laminitis?

Laminitis is a condition in horses that affects the blood supply and connective tissue from the bone to the hoof. In mild cases of laminitis there is just pain and inflammation which can be treated with rest, anti-inflammatories and special shoes to fit on the hoof.

Unfortunately, many times mild cases can progress to severe cases. There are also specific causes of laminitis that skip the mild phase and go right to the severe phase. The more severe phase can permanently damage the blood supply and the hoof would actually start to separate from the bone. If this happens many times it is irreversible and the only option for this is humane euthanasia. Stem cell therapy has been used to help to regrow the blood supply and connective tissue.

There are also reports that injecting adult stem cells harvested from bone marrow or fat can be used to treat arthritis in dogs and cats. There is a thin layer of cartilage that covers the bone at the joint called synovial cartilage. Synovial cartilage cushions the bone at the joint, as well as produces joint fluid. Joint fluid not only acts as a lubricant allowing the bones to slide back and forth, but also contains natural antioxidants and immune defenses.

When arthritis occurs in dogs the thin layers of synovial cartilage begin to degrade, or break down. It doesn’t happen all at once but when the cartilage is lost it does not grow back naturally. This is when you will hear orthopedists talk about “bone-on-bone” contact, and bone-on-bone contact is intensely painful.

The injection of stem cells into the joint has shown promise in regrowing this thin layer of synovial cartilage. No controlled studies have been performed to substantiate this claim. However, there are reports from various veterinarians using stem cells for this purpose that they see an improvement in their patients after receiving a stem cell treatment.

Using stem cells in veterinary patients to regrow tissue of any organ in the body is a long way off and even the use of stem cells for specific conditions like arthritis and laminitis has not been completely proven successful but there is hope on the horizon.

Source: http://www.northshoreoflongisland.com/Articles-i-2011-07-07-88828.112114-sub-Stem-cell-research-and-use-in-veterinary-medicine.html

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Who wants to live forever? Scientist sees aging cured

Last Updated on Tuesday, 5 July 2011 11:56 Written by admin Tuesday, 5 July 2011 11:56

(Reuters) – If Aubrey de Grey’s predictions are right, the first person who will live to see their 150th birthday has already been born. And the first person to live for 1,000 years could be less than 20 years younger.

A biomedical gerontologist and chief scientist of a foundation dedicated to longevity research, de Grey reckons that within his own lifetime doctors could have all the tools they need to “cure” aging — banishing diseases that come with it and extending life indefinitely.

“I’d say we have a 50/50 chance of bringing aging under what I’d call a decisive level of medical control within the next 25 years or so,” de Grey said in an interview before delivering a lecture at Britain’s Royal Institution academy of science.

“And what I mean by decisive is the same sort of medical control that we have over most infectious diseases today.”

De Grey sees a time when people will go to their doctors for regular “maintenance,” which by then will include gene therapies, stem cell therapies, immune stimulation and a range of other advanced medical techniques to keep them in good shape.

De Grey lives near Cambridge University where he won his doctorate in 2000 and is chief scientific officer of the non-profit California-based SENS (Strategies for Engineered Negligible Senescence) Foundation, which he co-founded in 2009.

He describes aging as the lifelong accumulation of various types of molecular and cellular damage throughout the body.

“The idea is to engage in what you might call preventative geriatrics, where you go in to periodically repair that molecular and cellular damage before it gets to the level of abundance that is pathogenic,” he explained.

CHALLENGE

Exactly how far and how fast life expectancy will increase in the future is a subject of some debate, but the trend is clear. An average of three months is being added to life expectancy every year at the moment and experts estimate there could be a million centenarians across the world by 2030.

To date, the world’s longest-living person on record lived to 122 and in Japan alone there were more than 44,000 centenarians in 2010.

Some researchers say, however, that the trend toward longer lifespan may falter due to an epidemic of obesity now spilling over from rich nations into the developing world.

De Grey’s ideas may seem far-fetched, but $20,000 offered in 2005 by the Massachusetts Institute of Technology (MIT) Technology Review journal for any molecular biologist who showed that de Grey’s SENS theory was “so wrong that it was unworthy of learned debate” was never won.

The judges on that panel were prompted into action by an angry put-down of de Grey from a group of nine leading scientists who dismissed his work as “pseudo science.”

They concluded that this label was not fair, arguing instead that SENS “exists in a middle ground of yet-to-be-tested ideas that some people may find intriguing but which others are free to doubt.”

CELL THERAPY

For some, the prospect of living for hundreds of years is not particularly attractive, either, as it conjures up an image of generations of sick, weak old people and societies increasingly less able to cope.

But de Grey says that’s not what he’s working for. Keeping the killer diseases of old age at bay is the primary focus.

“This is absolutely not a matter of keeping people alive in a bad state of health,” he told Reuters. “This is about preventing people from getting sick as a result of old age. The particular therapies that we are working on will only deliver long life as a side effect of delivering better health.”

De Grey divides the damage caused by aging into seven main categories for which repair techniques need to be developed if his prediction for continual maintenance is to come true.

He notes that while for some categories, the science is still in its earliest stages, there are others where it’s already almost there.

“Stem cell therapy is a big part of this. It’s designed to reverse one type of damage, namely the loss of cells when cells die and are not automatically replaced, and it’s already in clinical trials (in humans),” he said.

Stem cell therapies are currently being trialed in people with spinal cord injuries, and de Grey and others say they may one day be used to find ways to repair disease-damaged brains and hearts.

NO AGE LIMIT

Cardiovascular diseases are the world’s biggest age-related killers and de Grey says there is a long way to go on these though researchers have figured out the path to follow.

Heart diseases that cause heart failure, heart attacks and strokes are brought about by the accumulation of certain types of what de Grey calls “molecular garbage” — byproducts of the body’s metabolic processes — which our bodies are not able to break down or excrete.

“The garbage accumulates inside the cell, and eventually it gets in the way of the cell’s workings,” he said.

De Grey is working with colleagues in the United States to identify enzymes in other species that can break down the garbage and clean out the cells — and the aim then is to devise genetic therapies to give this capability to humans.

“If we could do that in the case of certain modified forms of cholesterol which accumulate in cells of the artery wall, then we simply would not get cardiovascular disease,” he said.

De Grey is reluctant to make firm predictions about how long people will be able to live in future, but he does say that with each major advance in longevity, scientists will buy more time to make yet more scientific progress.

In his view, this means that the first person who will live to 1,000 is likely to be born less than 20 years after the first person to reach 150.

“I call it longevity escape velocity — where we have a sufficiently comprehensive panel of therapies to enable us to push back the ill health of old age faster than time is passing. And that way, we buy ourselves enough time to develop more therapies further as time goes on,” he said.

“What we can actually predict in terms of how long people will live is absolutely nothing, because it will be determined by the risk of death from other causes like accidents,” he said.

“But there really shouldn’t be any limit imposed by how long ago you were born. The whole point of maintenance is that it works indefinitely.”

Source: http://www.reuters.com/article/2011/07/04/us-ageing-cure-idUSTRE7632ID20110704

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International Stem Cell Corporation Enrolls First Donor in Program to Create New Parthenogenetic Stem Cell Lines in the United States

Last Updated on Friday, 20 May 2011 02:04 Written by admin Friday, 20 May 2011 01:59

CARLSBAD, Calif.–(EON: Enhanced Online News)–International Stem Cell Corporation (OTCBB:ISCO), www.internationalstemcell.com, has now enrolled the first U.S.-based donor in its program to establish a bank of clinical-grade human parthenogenetic stem cells (hpSCs) capable of being immune-matched to millions of patients.

Dr. Simon Craw, Vice President of ISCO with primary responsibility for building its UniStemCell Bank, said, “Enrolling our first donor is a key milestone towards our goal of creating a bank of clinical-grade pluripotent human stem cells with the ability to immune-match millions of patients. It is extremely exciting to start this new phase of development, and I look forward to making new clinical-grade hpSC lines available to medical researchers around the world.”

ISCO maintains the world’s largest collection of research-grade human parthenogenetic stem cell (hpSC) lines which it uses along with its partners and collaborators to investigate cellular therapies for a number of incurable human diseases.

ISCO previously announced it had successfully obtained the necessary regulatory approvals for obtaining human oocytes, including Institutional Review Board (IRB) approval and Stem Cell Research Oversight (SCRO) committee approval. Today’s announcement marks the next phase of development as the Company is now positioned to begin producing new clinical-grade hpSC lines.

These new cell lines will be ISCO’s first hpSCs to be produced in the United States in accordance with Good Manufacturing Practice (cGMP) specifications. The new cGMP hpSC lines will be uniquely valuable in therapeutic research and clinical development as cells or tissue derived from such cells can be used in human clinical trials.

ISCO’s scientific discoveries have resulted in the development of a unique new type of pluripotent stem cells that possess a number of distinct advantages over other types of human pluripotent stem cells. ISCO uses unfertilized oocytes to create human “parthenogenetic” stem cells. Like human embryonic stem cells (hESCs), hpSCs are pluripotent, i.e. they have the capacity to become almost any cell type in the body, yet avoid ethical issues associated with use or destruction of viable human embryos. Unlike hESCs, hpSCs can be created in a form such that they can be immunologically matched to millions of individuals.

Source: http://eon.businesswire.com/news/eon/20110519005390/en

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Roche Allies with MGH and Harvard to Develop Stem Cell-Derived Cell Lines for Drug Discovery

Last Updated on Wednesday, 12 May 2010 01:26 Written by Editor Wednesday, 12 May 2010 01:26

Roche is teaming up with the Massachusetts General Hospital and Harvard University to develop new stem cell-based cell lines as disease models for early drug candidate testing. The 3â€“5 year partnership will initially focus on metabolic disorders and cardiovascular disease and will expand to cover a range of other diseases.

The collaboration aims to develop cell lines that can be used to evaluate the potential efficacy, safety, and toxicology profiles of new drugs pulled from Rocheâ€™s compound library. The company says that the cell lines will be derived from the tissues of both healthy volunteers and patients with a range of diseases.

Roche will provide research funding over the term of the agreement and will have access to cell lines, protocols, data, and materials. The firm will also pay clinical development milestones for drug candidates discovered through stem cell disease models.

The ultimate goal is to use stem cells for discovering new treatment approaches and bridging the gap between the laboratory and the clinic. â€œThis technology is like having a disease in a test tube and being able to test possible effects of drugs on virtual patientsâ€”translational medicine at its best,â€ states Jacques Garaud, global head of pharma research and early development at Roche.

Roche has forged a number of collaborations focused on evaluating stem cell-based approaches for drug discovery. In June 2009, the firm signed a â‚¬7.5 million (about $10.36 million), two-year collaboration with I-STEM (Institute for Stem Cell Therapy and Exploration of Monogenic Diseases) focused on the use of I-STEMâ€™s neuronal stem cell proliferation technologies in the screening of Rocheâ€™s compounds for potential new candidates against neurodegenerative diseases.

In 2008, Roche partnered with U.K.-based stem cell consortium SC4SM (Stem Cells 4 Safer Medicines) to generate a repository of stem cells suitable for toxicology testing in high-throughput platforms. The initiative is being fund primarily by the U.K. Government, with Roche and two other pharmaceutical companies also contributing. During the same year the firm signed an agreement with Cellular Dynamics to test a number of its drug compounds for cardiotoxicity.

source: genengnews.com

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Findings By Scripps Research Scientists Brighten Prospects Of Stem Cell Therapy For Range Of Diseases

Last Updated on Wednesday, 5 May 2010 10:44 Written by Editor Wednesday, 5 May 2010 10:44

A team led by scientists from The Scripps Research Institute has developed a method that dramatically improves the efficiency of creating stem cells from human adult tissue, without the use of embryonic cells. The research makes great strides in addressing a major practical challenge in the development of stem-cell-based medicine.

The findings were published in an advance, online issue of the journal Nature Methods on October 18, 2009.

The new technique, which uses three small drug-like chemicals, is 200 times more efficient and twice as fast as conventional methods for transforming adult human cells into stem cells (in this case called â€œinduced pluripotent stem cellsâ€ or â€œiPS cellsâ€).

â€œBoth in terms of speed and efficiency, we achieved major improvements over conventional conditions,â€ said Scripps Research Associate Professor Sheng Ding, Ph.D., who led the study. â€œThis is the first example in human cells of how reprogramming speed can be accelerated. I believe that the field will quickly adopt this method, accelerating iPS cell research significantly.â€

In addition to its significant practical advantages, the development of the technique deepens the understanding of the biology behind the transformation of adult human cells into stem cells.

Tackling Major Challenges

The hope of most researchers in the field is that one day it will be possible to use stem cells â€“ which possess the ability to develop into many other distinct cell types, such as nerve, heart, or lung cells â€“ to repair damaged tissue from any number of diseases, from Type 1 diabetes to Parkinsonâ€™s disease, as well as from injuries. The creation of iPS cells from adult cells sidesteps ethical concerns associated with the use of embryonic stem cells, and allows the generation of stem cells matched to a patientâ€™s own immune system, avoiding the problem of tissue rejection.

The creation of human iPS cells was first announced in December 2007 by two labs, one in Japan and another in Wisconsin. In both cases, the teams used viruses to insert multiple copies of four genes (eg. c-Myc, Oct4, Sox2, Klf4) into the genome of skin cells. These four genes then produced transcription factors turning on and off other genes, and pushing the cell to â€œdedifferentiateâ€ into stem cells.

While the work was a major breakthrough, it left two major challenges for the field to solve before iPS cell therapy could be considered of any potential practical use. The first involved safety, since the technique relied on potentially harmful genetic manipulation, and worse yet, the insertion of two known cancer-causing genes (c-Myc and Oct4). The second problem was the length and inefficiency of the iPS cell process, which had a success rate of roughly one in 10,000 cells and took about four weeks from start to finish.

Ding and colleagues essentially solved the first problem, the reliance on genetic manipulation, earlier this year in a paper published in Cell Stem Cell (Volume 4, Issue 5, May 8, 2009). In the paper, the researchers demonstrated that they could use purified proteins to transform adult cells all the way back to the most primitive embryonic-like cells, avoiding the problems associated with inserting genes.

In the current paper, the team makes major strides in solving the second problem, efficiency.

A Focus on Natural Processes

In developing the improved method, Ding drew on his knowledge of biology. He decided he would focus his efforts on manipulating a naturally occurring process in cells, in particular in a type of adult cell called fibroblasts, which give rise to connective tissue.

This naturally occurring process â€“ called MET (mesenchymal to ephithelial cell transition) â€“ pushes fibroblasts closer to a stem-cell-like state. If he could manipulate such a fundamental process to encourage MET and the formation of stem cells, Ding reasoned, such a method would be both safer and more direct than hijacking other aspects of biology, for example those directly involved in cancer.

â€œPeople have studied this mechanism for 10 to 20 years,â€ said Ding. â€œIt is a fundamental mechanism.â€

Ding and colleagues tested a number of drug-like molecules, looking for those that inhibited the TGFb (transforming growth factor beta) and the MEK (mitogen-activated protein kinase) pathways, which are known to be involved in the MET process. The researchers identified the most active compounds, then looked at their effects on stem cell creation when used singly and in combination.

The researchers found two chemicals â€“ ALK5 inhibitor SB43142 and MEK inhibitor PD0325901 â€“ used in combination were highly effective in promoting the transformation of fibroblasts into stem cells.

â€œThis method is the first in human cells that is mechanism-specific for the reprogramming process,â€ said Ding.

And the two-chemical technique bested the efficiency of the classic genetic method by 100 times.

Efficient, Fast, Safe

But the researchers thought they might be able to do even better.

Attempting to increase the efficiency of the process even further, the team decided to enlist another natural pathway, the cell survival pathway. After screening a library of compounds targeting this pathway, the team focused on a novel compound called Thiazovivin.

The researchers found that a technique using Thiazovivin in combination with the two previously selected chemicals, SB43142 and PD0325901, beat the efficiency of the classic method by 200 times.

In addition, while the classic method required four weeks to complete, the new method took two weeks.

In addition to its virtues of speed and efficiency, Ding emphasizes that the safety profile of the new method is highly promising. Not only is the method based on natural biological processes, he said, but also the type of molecules used have all been tested in humans. â€“ Scripps Research Institute

Posted under Press Releases, Stem Cell Research | Comments Off

Arno Therapeutics Announces Poster Presentation at ASH Annual Meeting Demonstrating Anti-Leukemic Stem Cell Activity of AR-42

Last Updated on Wednesday, 5 May 2010 10:28 Written by Editor Wednesday, 5 May 2010 10:28

PARSIPPANY, N.J. – (Business Wire) Arno Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on oncology therapeutics, today announced the presentation of a poster at the annual American Society of Hematology (ASH) meeting that describes the preclinical activity of Arnoâ€™s drug candidate AR-42 against leukemia stem cells (LSCs). AR-42 is a broad spectrum inhibitor of both histone and non-histone deacetylation proteins that demonstrated potent activity against Acute Myeloid Leukemia (AML) stem cells. The poster, entitled â€œIdentification of the Histone Deacetylase Inhibitor (HDACi), AR-42, as a Novel Anti-Leukemia Stem Cell Agent in Acute Myeloid Leukemia (AML)â€ was presented at the 51st ASH Annual Meeting and Exposition held December 5-8, 2009 in New Orleans, LA. LSCs are believed to be able to initiate and perpetuate AML while displaying resistance to standard chemotherapies. The ability to target these cells with therapeutic compounds may help improve patient outcomes. The posterâ€™s findings show that AR-42 preferentially targets LSCs compared to normal healthy cells. The research also suggests that AR-42 is active through a mechanism that differentiates it from other compounds with preclinical anti-LSC activity.

â€œThe ability to target cancer stem cells presents an opportunity to change the way that we treat patients, particularly those stricken with diseases that are currently difficult to cure,â€ stated Monica Guzman, Ph.D., a co-author of the poster with AR-42 at Weill Cornell Medical College. â€œPatients with AML are prone to recurrent disease, even if therapies are initially effective. Current evidence suggests that the survival of LSCs after treatment may ultimately contribute to the persistence of this disease and its poor clinical prognosis. Inhibiting LSCs may help treat and prevent recurrence of AML in patients.â€

â€œWe identified AR-42 by screening a large number of gene expression profiles from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) for potential anti-LSC agents. We were very excited to see our hypothesis confirmed both in vivo and in vitro, and we look forward to discovering if the same promising activity will be seen in the clinical setting,â€ said co-author Duane Hassane, Ph.D. of Weill Cornell Medical College.

â€œArno is very excited about the results from these recent studies and feels that this data helps to support our belief that AR-42 has the potential to emerge as a meaningful addition to the landscape of cancer therapies,â€ stated David Tanen, President of Arno.

About AR-42

AR-42 (formerly known as â€œHDAC-42â€) is an orally available, broad spectrum inhibitor of both histone and non-histone deacetylation proteins (â€œpan-DACâ€), which may both be important in cancer progression. Histone deacetylase (â€œHDACâ€) inhibitors are a growing class of compounds that target histone deactylase, a molecule involved in determining which genes are expressed in a particular cell. In preclinical studies, AR-42 has shown activity against a broad spectrum of deacetylation targets and increased potency compared to vorinostat (â€œSAHA,â€ or Zolinza^Â®), the first HDAC inhibitor to obtain FDA approval. Arno currently plans to commence an investigator-initiated Phase I/IIa study with AR-42 in collaboration with an academic institution in the first half of 2010.

About Arno Therapeutics

Arno Therapeutics, Inc. is a clinical-stage biopharmaceutical company that develops and commercializes innovative products for the treatment of cancer patients. Arnoâ€™s lead clinical compound, AR-12 (formerly known as â€œOSU-03012â€), is a potentially first-in-class, orally available, targeted anti-cancer agent that inhibits PDK-1, a protein in the PI3K/Akt pathway, and also causes cell death through the induction of endoplasmic reticulum stress. Arno is developing two additional drug candidates, AR-67 and AR-42. AR-67 is a novel, third-generation camptothecin analogue that inhibits topoisomerase I activity. AR-67 has demonstrated activity and an excellent safety profile in clinical studies as well as improved pharmacokinetic properties when compared to approved second-generation products Hycamtin^Â® (topotecan) and Camptosar^Â® (irinotecan). Arno is conducting a Phase II study of AR-67 in patients with Myelodysplastic Syndrome (MDS) who have failed prior therapies and anticipates commencing a Phase II study in patients with glioblastoma multiforme (GBM), a highly aggressive form of brain cancer by the end of this year.

For more information on Arno please visit www.arnothera.com.

Forward Looking Statements

This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding the timing, progress and anticipated results of the clinical development, regulatory processes, potential clinical trial initiations, potential IND and NDA filings, as well as our strategy, future operations, outlook, milestones, the success of Arnoâ€™s product development, future financial position, future financial results, plans and objectives of management, are forward-looking statements. We may not actually achieve these plans, intentions or expectations and Arno cautions investors not to place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Various important factors could cause actual results or events to differ materially from the forward-looking statements that we make. Such factors include, among others, risks that the results of clinical trials will not support our claims or beliefs concerning the effectiveness of our product candidates, our ability to finance the development of our product candidates, regulatory risks, and our reliance on third party researchers and other collaborators. Arno is providing this information as of the date of this presentation and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise.

Arno Therapeutics, Inc.
Brian Lenz, CPA, 862-703-7175
Chief Financial Officer
bl@arnothera.com

source: earthtimes.org

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Aeolus Drug Protects the Gastrointestinal Tract in Acute Radiation Syndrome Studies Sponsored by the National Institutes of Health`s National Institute for Allergy and Infectious Diseases

Last Updated on Wednesday, 2 December 2009 12:12 Written by Editor Wednesday, 2 December 2009 12:12

* AEOL 10150 Effectively Increases Regeneration of GI Stem Cells and Reduces the
Severity and Duration of Diarrhea
* Drug Improves Survival When Administered 24 Hours after Total Body
Irradiation

MISSION VIEJO, Calif.--(Business Wire)--
Aeolus Pharmaceuticals, Inc. (OTCBB: AOLS) announced today that recent
experiments in preclinical models conducted by the National Institutes of
Health`s (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
Radiation/Nuclear Medical Countermeasure Development program have shown that
AEOL 10150 can effectively increase regeneration of gastro-intestinal (GI) stem
cells, reduce the severity and duration of diarrhea and improve survival when
administered at 24 hours after doses of total-body irradiation that produce the
lethal GI syndrome. There are no published studies of agents that accomplish
this enhanced stem cell regenerative effect while maintaining GI function and
improving survival when administered post irradiation.

"The Aeolus drug AEOL 10150 passed our first phase of rigorous testing and
showed definitive effects on crypt stem cells and other secondary parameters
used to assess drug efficacy in ameliorating the acute GI syndrome," stated
Catherine Booth, Ph.D., Managing Director, Contract Research Services at
Epistem, Ltd. "This is one of few drugs shown to affect 'both' stem cell crypt
regeneration and survival in a syndrome that heretofore has been resistant to
mitigation with drugs administered at 24 hours post lethal exposure."

NIAID has a contract with the University of Maryland to provide product
development support services for the development of countermeasures against
radiation exposure. These studies are being conducted by Epistem, a
subcontractor of the University of Maryland, in compliance with criteria of the
FDA that are a pre-requisite for movement of the Aeolus drug along the pathway
for FDA licensure to treat lethally irradiated persons in the event of a
terrorist nuclear act. Epistem operates a major contract research organization
and provides services to identify novel drugs that can protect or improve the
repair of the gastrointestinal (GI) tract following exposure to irradiation and
performed these studies as part of its US NIH`s program for the screening of a
novel agents for bio-defense applications.

The NIH NIAID Radiation/Nuclear Medical Countermeasure Development program leads
the U.S. effort to develop treatments for radiation sickness following a nuclear
terrorist attack. GI-ARS is a massive, currently untreatable, problem following
high-dose, potentially lethal radiation exposure. Agents that mitigate these
effects would reduce sickness and hopefully prevent fatalities. The tests
performed by NIH/NIAID are also likely to identify agents with oncology
supportive care applications - agents that will reduce the severe ulceration and
diarrhea (mucositis) experienced by patients during radio- and chemo-therapy.
Risk of injury to the intestine is dose-limiting during abdominal and pelvic
radiation therapy-interventions that limit post-irradiation intestinal
dysfunction would have significant impact in large number of patients, estimated
to be between 1.5 to 2 million cancer survivors with post-irradiation intestinal
dysfunction. AEOL 10150 has previously demonstrated protective effects in
protecting healthy normal cells from damage occurring due to cancer radiation
therapy in preclinical models.

Radiation Damage to the GI Tract

The intestinal epithelium, a single layer of cells lining the surface of the GI
lumen, is responsible for vital functions of nutrient absorption, maintaining
fluid and electrolyte balance and protection of the body from bacteria,
bacterial toxins and non absorbed materials. The functional integrity of the GI
system is maintained via incessant production of epithelial cells from
specialized stem cells located in crypts at the base of the epithelium.
High-dose, total-body irradiation can result in a lethal GI syndrome that
results in significant morbidity and mortality within days consequent to killing
of the crypt stem cells and loss of the protective and absorptive epithelial
barrier. There are no FDA-approved drugs or biologics to treat the acute GI
syndrome.

About AEOL 10150

AEOL 10150 is a small molecule that catalytically consumes reactive oxygen and
nitrogen species (free radicals). The compound is a manganoporphyrin that
contains a positively-charged manganese metal ion that is able to accept and
give electrons to and from reactive oxygen species ("ROS") and reactive nitrogen
species ("RNS"). Research has shown that ROS and RNS have important cell
signaling roles, and through its interaction with RNS and ROS, AEOL 10150
appears to have multiple mechanisms of action including anti-oxidant,
anti-inflammatory and anti-angiogenic activities. In preclinical studies AEOL
10150 has demonstrated reductions in the markers for tissue hypoxia,
angiogenesis, inflammation and oxidative stress. Specifically, AEOL 10150 is
able to down-regulate oxidative stress and severe inflammation, which is
responsible for much of the tissue destruction that occurs as a result of
radiation exposure.

AEOL 10150 offers several unique advantages as a countermeasure for the
treatment of ARS, mustard gas and chlorine gas for civilian and military
populations. These include:

-- Flexible Treatment Paradigm - AEOL 10150 is intended for the treatment of
patients post-exposure, even in those who are already exhibiting symptoms,
eliminating the need for immediate administration in a predefined treatment
window. This approach has the added benefit of not requiring biodosimetry (a
means of laboratory analysis of the blood to determine the level of radiation
exposure).

-- Advanced Development Stage - AEOL 10150 has demonstrated safety in three
human clinical trials, and has an extensive pre-clinical safety and toxicology
package completed. The product also has an established stability profile that
permits long-term storage.

-- Large scale manufacturing - Aeolus has contract capacity with a large
manufacturing site to mass produce large quantities of AEOL 10150 under GMP
conditions.

-- Multiple Applications - AEOL 10150 has demonstrated protective effects
against radiation and mustard gas exposure, and within these indications has
shown the ability to treat multiple organ systems.

-- Commercial Application - Additionally, AEOL 10150 is being developed for use
as an adjunct to cancer radiation therapy, and preclinical data suggest that the
compound protects healthy normal cells from the effects of radiation without
compromising the efficacy of the radiation in killing tumor cells.

Potential for AEOL 10150 as a Countermeasure Against Multiple Terrorist Threats

AEOL 10150 has shown significant protective effects against radiation and
mustard gas in preclinical models. Additionally, based on its mechanism, it is
believed that the compound may potentially protect against exposure to chlorine
gas. Studies have been initiated to further explore AEOL 10150`s ability to
protect the lungs from damage due to exposure to mustard gas and chlorine gas. A
compound with the potential to protect against multiple threats would be of
significant benefit in both the military and civilian efforts to protect
citizens against potential threats. The FDA has a special rule under which
compounds may be approved for use against chemical and nuclear threats on the
strength of preclinical efficacy studies, which allows the potential for an
accelerated approval path versus conventional pharmaceutical applications.

About Aeolus Pharmaceuticals

Aeolus is developing a variety of therapeutic agents based on its proprietary
small molecule catalytic antioxidants, with AEOL 10150 being the first to enter
human clinical evaluation. AEOL 10150 is a patented, small molecule catalytic
antioxidant that mimics and thereby amplifies the body`s natural enzymatic
systems for eliminating reactive oxygen species, or free radicals. Studies
funded by the National Institutes for Health are currently underway evaluating
AEOL 10150 as a treatment for exposure to radiation, mustard gas and chlorine
gas. Additionally, the Company has funded mouse and non-human primate studies
necessary to seek approval of the compound as a treatment to protect and/or
mitigate radiation-induced damage to the lungs for which there are no
FDA-approved drugs. Radiation-induced pneumonits and/or fibrosis are potentially
lethal delayed effects of acute radiation exposure. The ability to control these
delayed consequences will also translate into the clinic and further emphasize
the dual utility of AEOL 10150.

About Epistem, Ltd.

Epistem is a biotechnology company commercializing its expertise in epithelial
stem cells in the areas of oncology, gastrointestinal diseases and
dermatological applications. Epistem develops innovative therapeutics and
biomarkers and provides contract research services to drug development
companies. The Group`s expertise is focused on the regulation of adult stem
cells located in epithelial tissue, which includes the gastrointestinal tract,
skin, hair follicles, breast and prostate. Epistem does not conduct research in
the areas of embryonic stem cells or stem cell transplantation. Epistem operates
three distinct business divisions, Contract Research Services, Novel Therapies
and Biomarkers.

Epistem`s Contract Research Services division provides scientific expertise and
preclinical research models to the NIH`s research programme on Radiation/Nuclear
Medical Countermeasure Development. This research programme, funded by the
National Institute of Allergy and Infectious Diseases through a contract with
the University of Maryland School of Medicine, tests drugs from early screening
through advanced development for the prevention and treatment of radiation
sickness following exposure to high dose radiation following a nuclear terrorist
attack. Epistem has developed its proprietary models to provide a unique insight
into the mechanisms of intestinal damage and repair following radiation
exposure. Epistem`s models evaluate the efficacy, mechanism of action, optimal
drug dosing and scheduling of potential new treatments. Epistem has an
eight-year track record of providing testing services to over 130 international
company clients in the United States, Europe, and Japan.

The statements in this press release that are not purely statements of
historical fact are forward-looking statements. Such statements include, but are
not limited to, those relating to Aeolus` product candidates, as well as its
proprietary technologies and research programs. Such forward-looking statements
involve known and unknown risks, uncertainties and other factors that may cause
Aeolus` actual results to be materially different from historical results or
from any results expressed or implied by such forward-looking statements.
Important factors that could cause results to differ include risks associated
with uncertainties of progress and timing of clinical trials, scientific
research and product development activities, difficulties or delays in
development, testing, obtaining regulatory approval, the need to obtain funding
for pre-clinical and clinical trials and operations, the scope and validity of
intellectual property protection for Aeolus` product candidates, proprietary
technologies and their uses, and competition from other biopharmaceutical
companies. Certain of these factors and others are more fully described in
Aeolus` filings with the Securities and Exchange Commission, including, but not
limited to, Aeolus` Annual Report on Form 10-K for the year ended September 30,
2008. Readers are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof.

Aeolus Pharmaceuticals, Inc.
John L. McManus
President and Chief Executive Officer
1-949-481-9825
Source: reuters.com

Copyright Business Wire 2009

Posted under Collaborations, Discoveries, Innovations and Patents, Drug Development, New Products, Press Releases, Research Projects, Stem Cell Research | Comments Off

Scripps research scientists take step in stem cell work

Last Updated on Tuesday, 1 December 2009 12:59 Written by Editor Tuesday, 1 December 2009 12:59

The findings were published in an advance, online issue of the journal Nature Methods on Sunday.

The new technique, which uses three small drug-like chemicals, is 200 times more efficient and twice as fast as conventional methods for transforming adult human cells into stem cells (in this case called “induced pluripotent stem cells” or “iPS cells”).

“Both in terms of speed and efficiency, we achieved major improvements over conventional conditions,” said Scripps Research Associate Professor Sheng Ding, Ph.D., who led the study. “This is the first example in human cells of how reprogramming speed can be accelerated. I believe that the field will quickly adopt this method, accelerating iPS cell research significantly.”

In addition to its significant practical advantages, the development of the technique deepens the understanding of the biology behind the transformation of adult human cells into stem cells.

The hope of most researchers in the field is that one day it will be possible to use stem cells – which possess the ability to develop into many other distinct cell types, such as nerve, heart, or lung cells – to repair damaged tissue from any number of diseases, from Type 1 diabetes to Parkinson’s disease, as well as from injuries. The creation of iPS cells from adult cells sidesteps ethical concerns associated with the use of embryonic stem cells, and allows the generation of stem cells matched to a patient’s own immune system, avoiding the problem of tissue rejection.

In the current paper, the team makes major strides in solving the second problem, efficiency.

This naturally occurring process – called MET (mesenchymal to ephithelial cell transition) – pushes fibroblasts closer to a stem-cell-like state. If he could manipulate such a fundamental process to encourage MET and the formation of stem cells, Ding reasoned, such a method would be both safer and more direct than hijacking other aspects of biology, for example those directly involved in cancer.

“People have studied this mechanism for 10 to 20 years,” said Ding. “It is a fundamental mechanism.”

Ding and colleagues tested a number of drug-like molecules, looking for those that inhibited the TGFï¢ (transforming growth factor beta) and the MEK (mitogen-activated protein kinase) pathways, which are known to be involved in the MET process. The researchers identified the most active compounds, then looked at their effects on stem cell creation when used singly and in combination.

The researchers found two chemicals – ALK5 inhibitor SB43142 and MEK inhibitor PD0325901 – used in combination were highly effective in promoting the transformation of fibroblasts into stem cells.

“This method is the first in human cells that is mechanism-specific for the reprogramming process,” said Ding.

And the two-chemical technique bested the efficiency of the classic genetic method by 100 times.

Efficient, Fast, Safe

But the researchers thought they might be able to do even better.

The researchers found that a technique using Thiazovivin in combination with the two previously selected chemicals, SB43142 and PD0325901, beat the efficiency of the classic method by 200 times.

In addition, while the classic method required four weeks to complete, the new method took two weeks.

In addition to Ding, the article, “A Chemical Platform for Improved Induction of Human iPS Cells,” was authored by Tongxiang Lin (first author), Rajesh Ambasudhan, Xu Yuan1, Wenlin Li, Simon Hilcove, Ramzey Abujarour, Xiangyi Lin, and Heung Sik Hahm of Scripps Research, and Ergeng Hao and Alberto Hayek of The Whittier Institute for Diabetes, University of California San Diego.

The research was supported by the National Institutes of Health and Fate Therapeutics.

Source: lajollalight.com

Posted under Press Releases, Research Projects, Stem Cell Research | Comments Off

Scientists get closer to making safe patient-specific stem cells

Last Updated on Monday, 30 November 2009 01:55 Written by Editor Monday, 30 November 2009 01:55

Scientists are a big step closer to their long-term of goal of creating patient-specific stem cells that are safe to use and donâ€™t require the destruction of embryos.

Induced pluripotent stem cells â€“ also known as iPS cells â€“ are all the rage in the nascent field of regenerative medicine. Like embryonic stem cells, they have the potential to become any type of cell in the body and could be used to grow replacement parts, such as insulin-producing beta cells for diabetes patients or nerve cells for repairing spinal cord injuries.

Even better, they can be made by reprogramming skin or other cells from the patients who need them. That not only eliminates the need to use embryos, it ensures that the replacement tissues made from iPS cells are genetically matched to patients and wonâ€™t be rejected by the bodyâ€™s immune system.

But thereâ€™s still a big catch: In order to rewind adult cells to a pluripotent state, researchers have to turn on a set of dormant genes that have the potential to cause tumors. So do the viruses they use to activate those genes.

So researchers have been looking for ways around this problem. One approach is to snip out the genes and viruses once the reprogramming is complete. Another is to use DNA sequences called transposons in place of viruses, then delete the transposons after theyâ€™re no longer needed. One group of researchers has even used genetic engineering to modify the key genes so that they can enter the skin cells without requiring viruses or transposons.

But many scientists think the safest approach is to replace the genes altogether with so-called small molecules. In a study published online today in the journal Cell Stem Cell, researchers from the Harvard Stem Cell Institute report that a single compound they dubbed RepSox can replace two of the four key reprogramming genes.

â€œWeâ€™re halfway home, and remarkably we got halfway home with just one chemical,â€ senior author Kevin Eggan, a professor in Harvardâ€™s department of stem cell and regenerative biology, said in a statement.

Egganâ€™s team identified RepSox by screening 200 compounds and waiting a couple of weeks to see which of them did the best job of transforming mouse cells into iPS cells in combination with three of the four reprogramming genes. The researchers were surprised to find that their compound not only replaced the gene Sox2 (hence the name RepSox), but also made the gene c-Myc obsolete.

Now the group will turn its attention to finding other small molecules that could replace the remaining genes â€“ Oct4 and Klf4 â€“ as well, â€œopening a route to purely chemical programming,â€ they write.

Posted under Compound Screening, Discoveries, Innovations and Patents, Press Releases, Stem Cell Research | Comments Off

The French Institute I-Stem Realizes First Innovative Screens Using Stem Cells to Identify Drugs for Myotonic Dystrophy

Last Updated on Friday, 20 March 2009 05:02 Written by Editor Friday, 20 March 2009 05:02

EVRY, France, March 19 /PRNewswire/ –Â Â Â Â Four research teams of I-STEM[*] have joined forces in a collaborative project that has just achieved a first pilot therapy-oriented screen of compounds and RNA interference aiming at reversing the altered phenotypes observed in human embryonic stem cells carrying the mutant gene for myotonic dystrophy type1. This assay inaugurates a series of R&D planned in 2009.Human embryonic stem (hES) cells lines carrying the mutant gene responsible for diseases may replicate associated molecular defects associated and be used, therefore, to analyse pathological mechanisms and search for treatments. I-STEM teams have shown that hES cell lines carrying the mutant gene responsible for myotonic dystrophy type1 (DM1) -the most frequent myopathy in adult- present known cellular and molecular abnormalities. hES capacity of self-renewal and pluripotency provides an unlimited and highly versatile cell resource, relevant for large-scale analyses. In order to exploit fully these potentials of hES cell lines within the framework of its exploration of therapeutics for monogenic diseases, I-STEM has set up a screening department through a close partnership with the companies Velocity11, Discngine and Prestwick Chemical. I-STEM has installed at its site, in Evry-Genopole, a powerful automation platform using the innovative Velocity11 BioCel1800(R) technology, coupled to a specific data management system designed by Discngine. The Conseil RÃ©gional d’Ile-de-France and the Association FranÃ§aise contre les Myopathies (thanks to the French Telethon donations) co-funded this platform[**]. The investments to buildÂ Â this facility assays have been developed in order to screen the “FDAÂ Â approved” Prestwick Chemical library and a subset of the in house designedÂ Â siRNA (small interferent RNA) library.

Using this screening platform, the I-STEM teams have looked for compounds and siRNA that would provoke the disruption of abnormal aggregation seen in the nucleus of human embryonic stem cells carrying the DM1 mutation. Several of the 1120 compounds and 50 siRNA assayed were identified as candidates.

I–STEM intends to perform five to ten similar screening campaigns per year on other genetic diseases, using its library of human stem cell lines carrying genetic mutations[***].

About I-STEM

The Institute for Stem Cells in the Treatment and Study of Monogenic Diseases- is a laboratory which has set out to explore the therapeutic potential of stem cells in the treatment of rare genetic diseases. Headed by Marc Peschanski (an INSERM Research Director), I-STEM was in early 2005, the first lab in France to be allowed to work on (imported) human embryonic stem cell lines. Then, in June 2006, it was authorized by the French Agency for Biomedicine to set up a library of mutated cell lines that can serve as models in the study of monogenic diseases. For more information: http://www.istem.eu

Posted under Collaborations, Compound Screening, Europe, Press Releases, RNA Reasearch, Stem Cell Research | Comments Off

International Symposium Stem Cell Transplantation in Multiple Sclerosis: Sharing the Experience in Moscow, Russia on the 5th of October, 2009

Last Updated on Friday, 23 January 2009 11:35 Written by admin Friday, 23 January 2009 11:34

The Symposium is focused on the new modality of multiple sclerosis treatmentâ€“ immunosuppressive therapy followed by autologous stem cell transplantation. Centers in Europe, North and South America, Russia, China, Israel and Australia have successfully performed this procedure, and, to date, more than 600 stem cell transplantations in multiple sclerosis have been performed worldwide.

Along with promising results there are a number of unclear and challenging issues that are worth studying.

The Symposium intends to share the newly acquired knowledge in the field, to discuss the challenges and perspectives of the method, and to develop collaborative projects. The topics to be covered within the symposium include:

Regimens of conditioning: Immunoablation or immunosupression?
Types of transplantation: autologous or allogenic?
Posttransplant immunological reconstitution
Side effects
Outcome measures: clinical, imaging, patient-reported outcomes
Posttransplant neurorehabilitation
Long-term follow-up results
Proposal for cooperative studies

We invite the submission of abstracts on the above aspects of stem cell transplantation in multiple sclerosis. All abstracts will be reviewed by an international committee and a number of abstracts will be selected for oral presentation within the Symposium.

www.stemcellms.ru

Posted under Cell Analysis, Europe, Europe, Press Releases, Stem Cell Research | Comments Off

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Archive for the ‘Stem Cell Research’ Category

First Clinical Trial of Autologous Cardiac Stem Cells Shows Positive Results

Scientists Use Mutant Protein to Inhibit Cancer Stem Cells and Resensitize Tumors to Lapatinib

Scientists Claim Differentiated Cancer Cells Can Convert to Stem-Like Cells to Maintain Equilibrium

Stem cell research and use in veterinary medicine

Who wants to live forever? Scientist sees aging cured

International Stem Cell Corporation Enrolls First Donor in Program to Create New Parthenogenetic Stem Cell Lines in the United States

Roche Allies with MGH and Harvard to Develop Stem Cell-Derived Cell Lines for Drug Discovery

Findings By Scripps Research Scientists Brighten Prospects Of Stem Cell Therapy For Range Of Diseases

Arno Therapeutics Announces Poster Presentation at ASH Annual Meeting Demonstrating Anti-Leukemic Stem Cell Activity of AR-42

Aeolus Drug Protects the Gastrointestinal Tract in Acute Radiation Syndrome Studies Sponsored by the National Institutes of Health`s National Institute for Allergy and Infectious Diseases

Scripps research scientists take step in stem cell work

Scientists get closer to making safe patient-specific stem cells

The French Institute I-Stem Realizes First Innovative Screens Using Stem Cells to Identify Drugs for Myotonic Dystrophy

International Symposium Stem Cell Transplantation in Multiple Sclerosis: Sharing the Experience in Moscow, Russia on the 5th of October, 2009

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