Stem Cell Clinic

Unusual 'altruistic' stem cell behavior with possible link to cancer identified

ScienceDaily (June 11, 2012) When most groups of mammalian cells are faced with a shortage of nutrients or oxygen, the phrase "every man for himself" is more apt than "all for one, one for all." Unlike colonies of bacteria, which often cooperate to thrive as a group, mammalian cells have never been observed to help one another out. But a new study led by a researcher at the Stanford University School of Medicine has shown that certain human embryonic stem cells, in times of stress, produce molecules that not only benefit themselves, but also help nearby cells survive.

"Altruism has been reported among bacterial populations and among humans and other animals, like monkeys and elephants," said Stanford postdoctoral scholar Bikul Das, MBBS, PhD. "But in mammalian cells -- at the cellular level -- the idea of altruism has never been described before." Das is the lead author of a paper, published online June 11 in Stem Cells, documenting altruistic behavior by human embryonic stem cells, or hESCs.

While altruism is generally thought of as a virtue, it can have a downside for hESCs: The altruistic cells appear to be more prone to accumulating mutations, a sign that they could lead to cancers. A better understanding of hESC altruism could provide new insights into cancer therapies, as well as improving scientists' ability to develop safe and effective stem cell treatments for other diseases.

The finding arose from Das' research into how hESCs react to low-oxygen environments, important because many cancerous tumors are low in oxygen. Embryonic stem cells have the capability to develop into many different cell types through a process called differentiation. Das found that when hESCs were placed for 24 hours in an environment with only one-tenth of a percent of oxygen (the air we breathe, by comparison, is almost 21 percent oxygen), free-radical molecules were generated that began causing internal damage in some cells. Ninety percent of the hESCs differentiated into other cell types or died, with only 10 percent maintaining their so-called "stemness," meaning they retained their ability to develop into any type of cell.

Das wanted to know what set these more hearty cells apart and so began sorting them based on what molecules they contained.

Das and his colleagues discovered that of the embryonic stem cells that had survived the oxygen deprivation, half had high levels of HIF2-alpha (a protein that turns up the production of antioxidant molecules) and low levels of p53 (a protein that normally encourages cells to die when they have too much DNA damage). These levels of HIF2-alpha and p53 are enough, Das showed, to keep the cells from differentiating by turning off cellular pathways typically involved in the process.

But the other half of the stem cells that had kept their "stemness" had relatively normal levels of HIF2-alpha and p53, he and his colleagues report in their paper. There was no clear explanation as to how they would remain undifferentiated without the help of high HIF2-alpha and low p53 -- unless the other cells were helping them out.

"When I saw this data, I began to suspect that maybe there was altruism going on," said Das.

To test the theory, Das and his colleagues at the University of Toronto, where he began the work as a graduate student, let the cells with high levels of HIF2-alpha and low levels of p53 soak in a cell culture medium for 24 hours. Then, he removed the cells and added the other half -- those that didn't have high HIF2-alpha and low p53. Sure enough, when the mixture was deprived of oxygen, the cells retained their stemness. Molecules in the liquid had some property that kept them from differentiating. The team discovered that the important molecule in the liquid is an antioxidant called glutathione.

Scientists had previously shown that when embryonic stem cells are under stress, levels of HIF2-alpha and p53 increase and most cells differentiate or die. What makes this study unusual is that Das and colleagues were able to isolate the altruistic cells that exhibit low levels of p53, which helps them to escape death or differentiation.

See original here:
Unusual 'altruistic' stem cell behavior with possible link to cancer identified

Fate Therapeutics And BD Biosciences Launch BD™ SMC4 To Improve Cellular Reprogramming And IPS Cell Culture Applications

SAN DIEGO, June 11, 2012 /PRNewswire/ --Fate Therapeutics, Inc. in collaboration with BD Biosciences, a segment of BD (Becton, Dickinson and Company), today announced the introduction of the first induced pluripotent stem cell (iPSC)-related product resulting from the collaboration between the two companies. BD SMC4 is a patent protected, pre-formulated cocktail of small molecules for improving cellular reprogramming efficiencies and for enabling single-cell passaging and flow cytometry sorting of iPSCs in feeder cell-free and other pluripotent cell culture systems.

"iPSCs have the potential to redefine the way medical research is conducted," said Dr. Charles Crespi, Vice President at BD Biosciences. "However, most current reprogramming technologies are inefficient, which slows research efforts. BD SMC4 is an exciting complement to the BD portfolio of stem cell technologies that can accelerate the pace of research, and, ultimately, drug development."

The collaboration between BD Biosciences and Fate Therapeutics seeks to provide life science researchers and the pharmaceutical community reliable access to advanced iPSC tools and technologies. These technologies are for use in human disease research, drug discovery and the manufacture of cell-based therapies. The identification of the small molecule additives, and their use in an industrial platform for iPSC generation and characterization was recently published in the journal, Scientific Reports (Valamehr et al Scientific Reports 2, Article number: 213, 2012).

"Our research focus has uncovered novel technologies to enable the commercial and industrial application of iPS cells," said Dr. Peter Flynn, Vice President of Biologic Therapeutics at Fate Therapeutics. "The BD SMC4 media additive was developed at Fate to enable our scientists to internally perform high-throughput generation, clonal selection, characterization and expansion of pluripotent cells, and we are excited to empower the stem cell research community with these important iPSC technologies through our collaboration with BD."

iPSC technology holds great promise for disease modeling, drug screening and toxicology testing as well as for autologous and allogeneic cell therapy. Building on the foundational work of its scientific founders, Drs. Rudolf Jaenisch and Sheng Ding, Fate Therapeutics is developing a suite of proprietary products and technologies to overcome the remaining technical hurdles for iPS cell integration into the therapeutic development process. Under the three-year collaboration, Fate and BD will co-develop certain stem cell products using Fate's award-winning iPSC technology platform, and BD will commercialize these stem cell products on a worldwide basis. The iPSC product platform of Fate Therapeutics is supported by foundational intellectual property including U.S. Patent No. 8,071,369, entitled "Compositions for Reprogramming Somatic Cells," which claims a composition comprising a somatic cell having an exogenous nucleic acid that encodes an Oct4 protein introduced into the cell.

About Fate Therapeutics, Inc. Fate Therapeutics is an innovative biotechnology company developing novel stem cell modulators (SCMs), biologic or small molecule compounds that guide cell fate, to treat patients with very few therapeutic options. Fate Therapeutics' lead clinical program, ProHema, consists of pharmacologically-enhanced hematopoietic stem cells (HSCs), designed to improve HSC support during the normal course of a stem cell transplant for the treatment of patients with hematologic malignancies. The Company is also advancing a robust pipeline of human recombinant proteins, each with novel mechanisms of action, for skeletal muscle, beta-islet cell, and post-ischemic tissue regeneration.Fate Therapeutics also applies its award-winning, proprietary induced pluripotent stem cell (iPSC) technology to offer a highly efficient platform to recapitulate human physiology for commercial scale drug discovery and therapeutic use. Fate Therapeutics is headquartered in San Diego, CA, with a subsidiary in Ottawa, Canada. For more information, please visit http://www.fatetherapeutics.com.

About BDBD is a leading global medical technology company that develops, manufactures and sells medical devices, instrument systems and reagents. The Company is dedicated to improving people's health throughout the world. BD is focused on improving drug delivery, enhancing the quality and speed of diagnosing infectious diseases and cancers, and advancing research, discovery and production of new drugs and vaccines. BD's capabilities are instrumental in combating many of the world's most pressing diseases. Founded in 1897 and headquartered in Franklin Lakes, New Jersey, BD employs approximately 29,000 associates in more than 50 countries throughout the world. The Company serves healthcare institutions, life science researchers, clinical laboratories, the pharmaceutical industry and the general public. For more information, please visit http://www.bd.com.

SOURCE Fate Therapeutics, Inc.

See the rest here:
Fate Therapeutics And BD Biosciences Launch BD™ SMC4 To Improve Cellular Reprogramming And IPS Cell Culture Applications

New details in Grekos patient death case

BONITA SPRINGS -

An attorney for the Bonita Springs doctor accused of performing controversial stem cell treatment on a patient who then died expects depositions to be taken this week that he says will help clear his client's name.

Dr. Zannos Grekos had his medical license suspended back in March after a patient, 77-year-old Richard Poling, died following an injection of his own stem cells.

Documents posted on the Department of Health's website show that Poling paid $8,000 by wire transfer to have his own stem cells removed from his body and sent by courier to a lab in Boynton Beach. The cells were to be processed and returned the same day.

According to the documents, Poling had stomach pains before his cells were returned. Doctors discovered the man had a hematoma, and made him comfortable while he waited for his tissue to be returned for re-injection.

The Department of Health found the laboratory used to process the cells "turned out to be a small office in a strip mall" and "the person that allegedly operated the machine that performed the ultrasonic cavitation on the sample of R.P.'s tissue was unsupervised and was not licensed either by the Florida Board of Medicine or by the Florida Board of Clinical Laboratory Personnel."

Further, documents state the stem cell material was not tested, only visually inspected before being brought back to Bonita Springs.

Poling went into cardiac arrest as the cells were injected into his body.

The Department of Health report states the stem cells were found during autopsy in the pulmonary arteries and capillaries.

Grekos' attorney says the clinician who worked at the Boynton Beach lab did not need a license. He tells NBC2 the clinician and an assistant will be interviewed this week by the Department of Health. Department officials have not confirmed that information.

Go here to see the original:
New details in Grekos patient death case

Experimental Stem Cell Treatment Tested for Type 1 Diabetes

In Early Study, Procedure Helps Teens Halt Insulin Injections

June 11, 2012 (Philadelphia) -- In an early study, an experimental stem cell procedure helped 15 teens with type 1 diabetes stay off of insulin injections for about 1.5 years, on average.

The study was very small, and the procedure is not ready for widespread use. "We now have a unique approach with some positive findings, but it's still early. We need to better understand the biology behind the treatment and follow patients for long-term side effects," Robert E. Ratner, MD, chief scientific and medical officer of the American Diabetes Association, tells WebMD.

This is the latest of several stem cell studies to show promising results for the treatment of type 1 diabetes, Ratner notes.

In the new study, 15 of 28 teens with type 1 diabetes who got an experimental treatment using their own stem cells went into remission and did not need insulin injections for an average of about 1.5 years.

The "cocktail treatment" combines stem cell therapy with drugs that suppress the body's immune system. In type 1 diabetes, the immune system attacks and destroys insulin-producing cells within the pancreas.

The experimental treatment is called autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT). It aims to kill the destructive immune system cells and replace them with immature stem cells not programmed to destroy insulin-producing cells.

First, patients are given drugs to stimulate production of blood stem cells. The blood stem cells are then removed from the body and frozen. Then, patients are hospitalized and given drugs to kill the destructive immune system cells. The harvested blood stem cells are then put back into the patient.

Eight teens who took part in the study have remained insulin-free for two years, on average. One patient has gone without insulin injections for 3.5 years.

"All our patients considered the [treatment] to be worthwhile and beneficial, though some patients experienced side effects," study head Weiqiong Gu, MD, of Ruijin Hospital in Shanghai, tells WebMD.

See the rest here:
Experimental Stem Cell Treatment Tested for Type 1 Diabetes

ZIOPHARM Oncology Announces Dosing of First Patient in Phase 3 Study of Palifosfamide for the Treatment of Small Cell …

NEW YORK, June 11, 2012 (GLOBE NEWSWIRE) -- ZIOPHARM Oncology, Inc. (ZIOP), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, today announced that the first patient has been dosed in the MATISSE study (Multicenter Adaptive Trial Investigating Small cell lung cancer Survival Endpoints), a pivotal Phase 3 multi-center, open-label, adaptive, randomized study of palifosfamide for the treatment of small cell lung cancer. ZIOPHARM has also recently announced the completion of enrollment in its Phase 3 study of palifosfamide in combination with doxorubicin for the treatment of metastatic soft tissue sarcoma in the front-line setting (PICASSO 3).

The MATISSE study is designed to enroll up to 548 chemotherapy naive patients with extensive-stage small cell lung cancer. Eligible patients will be randomized, one-to-one, to receive either palifosfamide in combination with carboplatin and etoposide (PaCE) or carboplatin and etoposide alone. The trial's primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate and quality of life. MATISSE will be conducted at centers in North America, Europe, Australia and Asia.

"Small cell lung cancer is an extraordinarily difficult to treat cancer, for which there has been no novel treatment in decades," said Lawrence Einhorn, M.D., Distinguished Professor at the Simon Cancer Center of Indiana University Medical Center, Lance Armstrong Foundation Chair in Oncology, former President of ASCO and a member of ZIOPHARM's Medical Advisory Board. "An important element of treating the disease is to find an agent that is safe and has minimal variability between patients. Palifosfamide has demonstrated broad therapeutic activity, including effects against cancer stem cells, as well as good tolerability alone and in combination with various chemotherapeutics. MATISSE incorporates a novel, adaptive study design that should provide a clinically meaningful understanding of palifosfamide's activity and tolerability in advanced disease as quickly as possible for this heavily underserved population."

The study's adaptive design includes a prospectively planned opportunity for modification of the study protocol by adjusting one or more specified components of the design in order to maintain adequate power. Evaluation of the study's powering will be conducted by an Independent Data Monitoring Committee (IDMC) at a single, pre-planned interim analysis, scheduled to occur following 125 events. At the interim analysis, the IDMC will review all efficacy and safety data and decide whether to: 1) halt the study for efficacy or futility, 2) continue the study to its planned enrollment of 548 patients, 3) decrease sample size, or 4) increase event size.

The MATISSE study is designed around clinical data from several studies of palifosfamide, including a Phase 1b, open-label, dose escalation study of intravenous palifosfamide in combination with etoposide and carboplatin in patients with SCLC and other selected cancers, which demonstrated good tolerability and a clinical benefit rate of 67%. Data from a Phase 3 randomized study of ifosfamide, an in-class DNA-targeted anti-cancer therapy, conducted by the Hoosier Oncology Group (HOG) were also incorporated in to the efficacy rationale for the MATISSE study. In this HOG study, ifosfamide demonstrated a survival benefit, the only front-line therapy added to standard of care to do so in SCLC, but was not pursued due to the excessive toxicities.

About Small Cell Lung Cancer

Small cell lung cancer is almost exclusively associated with cigarette smoking, and the majority of patients with extensive disease are treated front-line but relapse with a very high mortality within one year. According to the American Cancer Society, approximately 15 percent of lung cancers are SCLC, or an incidence of approximately 33,400 patients yearly in the U.S. There is expected to be a substantially growing incidence worldwide.

About ZIOPHARM Oncology, Inc.:

ZIOPHARM Oncology is a biopharmaceutical company focused on the development and commercialization of new cancer therapies. The Company's clinical programs include:

Palifosfamide (ZIO-201), a novel DNA-targeted cancer treatment that bypasses drug resistance mediated by ALDH (aldehyde dehydrogenase), an enzyme associated with cancer stem cells, and has a favorable toxicity profile. Intravenous palifosfamide is currently being studied in a randomized, double-blinded, placebo-controlled Phase 3 trial (PICASSO 3) for the treatment of front-line metastatic soft tissue sarcoma and is also in a pivotal Phase 3 trial (MATISSE) for front-line metastatic small cell lung cancer. Additionally, the Company is developing an oral capsule form of palifosfamide.

View original post here:
ZIOPHARM Oncology Announces Dosing of First Patient in Phase 3 Study of Palifosfamide for the Treatment of Small Cell ...

Research and Markets: Analysis of the Stem Cell Markets-Unlocking the New Era in Therapeutics

DUBLIN--(BUSINESS WIRE)--Research and Markets (http://www.researchandmarkets.com/research/pqrlwc/analysis_of_the_st) has announced the addition of Frost & Sullivan's new report "Analysis of the Stem Cell Markets-Unlocking the New Era in Therapeutics" to their offering.

Analysis of the Stem Cell Markets-Unlocking the New Era in Therapeutics

This Frost & Sullivan research service titled Analysis of the Stem Cell Markets-Unlocking the New Era in Therapeutics focuses on prospects for the stem cell therapeutics market in Europe and provides valuable recommendations and conclusions for market participants. Market segmentation is based on regulatory framework in Europe relating to research on adult and embryonic stem cells. The main countries discussed are the United Kingdom, Germany, France, Spain, Sweden, Finland, and the remaining parts of Europe.

Market Overview

New Applications in Drug Discovery Platforms to Drive Stem Cells Market

Stem cells offer exciting potential in regenerative medicine, and are likely to be widely used by mid-2017. Pharmaceutical, biotech and medical device companies are showing increased interest in stem cell research. The market will be driven by stem cell applications in drug discovery platforms and by successful academia -commercial company partnership models.

The high attrition rates of potential drug candidates has piqued the interest of pharmaceutical and biotech industries in stem cell use during the drug discovery phase, notes the analyst of this research. Previously, animal cell lines, tumours, or genetic transformation have been the traditional platform for testing drug candidates; however, these abnormal' cells have significantly contributed to a lack of translation into clinical studies. Many academic institutes and research centres are collaborating with biotechnology and pharmaceutical companies in stem cell research. This will provide impetus to the emergence of novel cell-based therapies.

Host of Challenges Need to be Confronted before Stem Cell Therapeutics can Realise its Potential

Key challenges to market development relate to reimbursement, ethics and the complexity of clinical trials. Securing reimbursement for stem cell therapeutic products is expected to be critical for commercial success. However, stem cell therapies are likely to be expensive. Insurers, therefore, may be unwilling to pay for the treatment. At the same time, patients are unlikely to be able to afford these treatments. The use of embryonic stem cells raises a host of thorny ethical, legal, and social issues, adds the analyst. As a result, market prices for various products may be affected. Moreover, many research institutes are adopting policies promoting the ethical use of human embryonic tissues. Such policies are hindering the overall research process for several companies working in collaboration with these institutes.

In addition to apprehensions about how many products will actually make it through human-based clinical trials, companies are also worried about which financial model can be applied to stem cell therapies, cautions the analyst. Possibly low return on investment (ROI) is also resulting in pharmaceutical companies adopting a cautious approach to stem cell therapeutics. To push through policy or regulatory reforms, the technology platform and geographical location of stem cell companies should complement the terms laid down in EMEA. The methodology for cell expansion and synchronisation must be optimised to acquire a large population of the desired cell at the right differentiation point, adds the analyst. More research is needed in human pluripotent and multi potent stem cell as it differs from mice to humans. Completion of clinical trials will be essential to ensure the safety and efficacy of the stem cell therapy.

Continue reading here:
Research and Markets: Analysis of the Stem Cell Markets-Unlocking the New Era in Therapeutics