Mount Sinai discovers new liver cell for cellular therapy to aid in liver regeneration

Public release date: 6-Jun-2013 [ | E-mail | Share ]

Contact: Renatt Brodsky newsmedia@mssm.edu 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

Liver transplantation is the mainstay of treatment for patients with end-stage liver disease, the 12th leading cause of death in the United States, but new research from the Icahn School of Medicine at Mount Sinai, published in the online journal Cell Stem Cell today, suggests that it may one day become possible to regenerate a liver using cell therapy in patients with liver disease. Investigators discovered that a human embryonic stem cell can be differentiated into a previously unknown liver progenitor cell, an early offspring of a stem cell, and produce mature and functional liver cells.

"The discovery of the novel progenitor represents a fundamental advance in this field and potentially to the liver regeneration field using cell therapy," said the study's senior author, Valerie Gouon-Evans, PharmD, PhD, Assistant Professor, in the Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, at the Icahn School of Medicine at Mount Sinai. "Until now, liver transplantation has been the most successful treatment for people with liver failure, but we have a drastic shortage of organs. This discovery may help circumvent that problem."

In conjunction with the laboratory of Matthew J. Evans, PhD, from the Department of Microbiology at Icahn School of Medicine at Mount Sinai, investigators demonstrated the functionality of the liver cells generated from the progenitors, as the liver cells can be infected by the hepatitis C virus, a property restricted to liver cells exclusively.

A critical discovery in this research was finding that the novel progenitor has a receptor protein on its cell surface called KDR, or vascular endothelial growth factor receptor 2, which until now, was thought to be restricted to endothelial cells that form vessels, the progenitors for endothelial cells and the progenitors blood cells. The research team showed that activation of KDR on these novel liver progenitors differentiates them into mature liver cells. Additionally, work in a mouse model revealed similar cells, indicating that the progenitors are conserved from mouse to human, and therefore, they must be "important cells with promising potential for cell therapy in treating liver disease," explained Dr. Gouon-Evans.

Next, the research team will examine specifically whether these liver cells obtained from human embryonic stem cells in a dish help repair injured livers in preclinical animal models of liver disease.

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Funding for this study was provided by The Black Family Stem Cell Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Robin Chemers Neustein Postdoctoral Fellowship, the American Cancer Society, and Pew Charitable Funds.

About the Black Family Stem Cell Institute

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Mount Sinai discovers new liver cell for cellular therapy to aid in liver regeneration

New liver cell for cellular therapy to aid in liver regeneration

June 6, 2013 Liver transplantation is the mainstay of treatment for patients with end-stage liver disease, the 12th leading cause of death in the United States, but new research from the Icahn School of Medicine at Mount Sinai, published in the journal Cell Stem Cell today, suggests that it may one day become possible to regenerate a liver using cell therapy in patients with liver disease. Investigators discovered that a human embryonic stem cell can be differentiated into a previously unknown liver progenitor cell, an early offspring of a stem cell, and produce mature and functional liver cells.

"The discovery of the novel progenitor represents a fundamental advance in this field and potentially to the liver regeneration field using cell therapy," said the study's senior author, Valerie Gouon-Evans, PharmD, PhD, Assistant Professor, in the Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, at the Icahn School of Medicine at Mount Sinai. "Until now, liver transplantation has been the most successful treatment for people with liver failure, but we have a drastic shortage of organs. This discovery may help circumvent that problem."

In conjunction with the laboratory of Matthew J. Evans, PhD, from the Department of Microbiology at Icahn School of Medicine at Mount Sinai, investigators demonstrated the functionality of the liver cells generated from the progenitors, as the liver cells can be infected by the hepatitis C virus, a property restricted to liver cells exclusively.

A critical discovery in this research was finding that the novel progenitor has a receptor protein on its cell surface called KDR, or vascular endothelial growth factor receptor 2, which until now, was thought to be restricted to endothelial cells that form vessels, the progenitors for endothelial cells and the progenitors blood cells. The research team showed that activation of KDR on these novel liver progenitors differentiates them into mature liver cells. Additionally, work in a mouse model revealed similar cells, indicating that the progenitors are conserved from mouse to human, and therefore, they must be "important cells with promising potential for cell therapy in treating liver disease," explained Dr. Gouon-Evans.

Next, the research team will examine specifically whether these liver cells obtained from human embryonic stem cells in a dish help repair injured livers in preclinical animal models of liver disease.

Funding for this study was provided by The Black Family Stem Cell Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Robin Chemers Neustein Postdoctoral Fellowship, the American Cancer Society, and Pew Charitable Funds.

About The Black Family Stem Cell Institute The Black Family Stem Cell Institute is Mount Sinai's foundation for both basic and disease-oriented research on embryonic and adult stem cells. The therapeutic use of stem cells is a promising area of medicine for the decades ahead and researchers are examining why stem cells function in certain types of niches, microenvironments, and pockets of activity. Investigators are working to break the code in stem cell communication by determining how stem cells signal one another and other cells. The new knowledge that will result from this research holds the promise of diagnostic and therapeutic breakthroughs.

Studies show that it is possible to reprogram adult skin cells into cells that are very similar to embryonic stem cells. Once stem cells can be grown and differentiated in a controlled way to replace degenerated cells and repair tissues, medical science may then be able to diagnose and cure many intractable diseases at their earliest stages, such as type 1 diabetes, Parkinson's disease, various cardiovascular diseases, liver disease, and cancer.

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New liver cell for cellular therapy to aid in liver regeneration

Singer targets stem cell donors

4 June 2013 Last updated at 14:32 ET By David Cornock BBC Wales Parliamentary correspondent

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Mike Peters played at parliament as some MPs signed the donor register

Mike Peters is a survivor. Lead singer of The Alarm since 1981, he's had 15 UK Top 40 hits and sold more than five million records.

He's also a cancer survivor, twice, and in that role he came to parliament today as part of a drive to increase the number of stem cell donors.

A day after receiving chemotherapy treatment near his home in north Wales, he headed to Westminster for the launch of "Get On The List", a campaign to recruit potential donors.

MPs were targeted at a donor registration event in the hope that they would encourage others to register to help blood cancer patients.

The campaign sees Peters' Love Hope Strength Foundation join forces with Delete Blood Cancer UK charity, which says that half the people in Britain who need a life-saving stem cell donor don't actually find a suitable match.

People are realising that one day it could be someone that they know who needs a stem cell donor,

The register is open to anyone between the ages of 17 and 55, if they are in good general health. Fans of The Alarm have been recruited during the band's tours.

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Singer targets stem cell donors

Test to improve stem cell safety

Public release date: 3-Jun-2013 [ | E-mail | Share ]

Contact: Simon Hunter Simon.Hunter@csiro.au 61-395-458-412 CSIRO Australia

CSIRO scientists have developed a test to identify unsafe stem cells. It is the first safety test specifically for human induced pluripotent stem cells (iPS) as published today in the international journal Stem Cells.

The breakthrough is a significant step in improving the quality of iPS cells and identifying unwanted cells that can form tumours. The test also determines how stable iPS cells are when grown in the lab. Dr Andrew Laslett and his team have spent the last five years working on the project. The research has focused on comparing different types of iPS cells with human embryonic stem cells. iPS cells are now the most commonly used pluripotent stem cell type for research.

"The test we have developed allows us to easily identify unsafe iPS cells. Ensuring the safety of these cell lines is paramount and we hope this test will become a routine screen as part of developing safe and effective iPS-based cell therapies," says Dr Laslett.

Using their test method, Dr Laslett's team has shown that certain ways of making iPS cells carry more risks. When the standard technique is used, which relies on viruses to permanently change the DNA of a cell, unwanted tumours are more likely to form. In comparison, cells made using methods which do not alter cell DNA, do not form tumours.

Dr Laslett hopes the study and the new test method will help to raise the awareness and importance of stem cell safety and lead to improvements in quality control globally.

"It is widely accepted that iPS cells made using viruses should not be used for human treatment, but they can also be used in research to understand diseases and identify new drugs. Having the assurance of safe and stable cells in all situations should be a priority," says Dr Laslett.

The test uses laser technology to identify proteins found on the surface of the cells. Based on the presence or absence of specific proteins the cells are then separated and monitored. Unsafe stem cell lines are easily identified because they form recognisable clusters of cells and the safe ones don't. This test could also be applied to assess the safety of the recently announced somatic cell nuclear transfer human embryonic stem cells.

Professor Martin Pera, Program Leader of Stem Cells Australia, said: "Although cell transplantation therapies based on iPS cells are being fast-tracked for testing in humans, there is still much debate in the scientific community over the potential hazards of this new technology."

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Test to improve stem cell safety

Stem cell study could aid quest to combat range of diseases

June 3, 2013 Scientists have taken a vital step forward in understanding how cells from skin tissue can be reprogrammed to become stem cells.

New research could pave the way to generate these stem cells efficiently to better understand and develop treatments for diseases such as multiple sclerosis, Parkinson's disease and muscular degeneration.

The study of how these cells -- known as induced pluripotent stem cells (iPSCs) -- were reprogramed was led by the University of Edinburgh and is published in the journal Nature.

Scientists found that the process by which iPSCs are created is not simply a reversal of how skin cells are generated in normal human development.

Researchers made the discovery by tracking the change of skin cells during the reprogramming process.

All cells in the human body begin life as a mass of cells, with the capacity to change into any specialised cell, such as skin or muscle cell.

By returning adult cells to this original state and recreating the cell type needed for treatment scientists hope to find ways of tackling diseases such as MS, in which cells become faulty and need to be replaced.

Scientists have been able to create stem cells in this way since 2006 but, until now, it has not been clear how adult cells 'forget' their specialised roles to be reprogrammed by scientists.

Experts say that current methods of iPSCs production are time consuming and costly. It takes around four weeks to make human stem cells and even then the process does not always work.

Researchers say that their new insight will enable them to streamline the stem cell production process. The finding may also shed light on how to create different cell types -- like muscle or brain cells -- that can be used to improve our understanding of diseases and treatment.

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Stem cell study could aid quest to combat range of diseases

Stem Cell Therapeutics' Clinical Advisor and Collaborator Receives Prestigious National Award

TORONTO, ONTARIO--(Marketwired - Jun 4, 2013) - Stem Cell Therapeutics Corp. (TSX VENTURE:SSS) (SCTPF), a biopharmaceutical company developing cancer stem cell-related therapeutics, today announced that Dr. Aaron Schimmer has been awarded a prestigious national award for his groundbreaking cancer research for the second time in approximately a year.

Each year, the Canadian Cancer Society honours four exceptional Canadian scientists who have made significant contributions to progress in cancer research. This year, Dr. Schimmer is the recipient of the Bernard and Francine Dorval Prize, which is awarded to a promising investigator who began their independent research within the previous 10 years and who has made outstanding contributions to basic biomedical research. In 2012, Dr. Schimmer received the Till & McCulloch Award, presented each year by the Stem Cell Network in recognition of the year's most influential peer-reviewed article by a researcher in Canada.

Dr. Schimmer's laboratory is investigating the repurposing of several FDA-approved drugs with favourable pharmacokinetic and toxicological properties for use as novel anticancer agents. One of these drugs is tigecycline, a broad-spectrum antibiotic. Stem Cell Therapeutics ("SCT") recently acquired exclusive worldwide rights to an innovative clinical cancer stem cell program based on Dr. Schimmer's discovery that tigecycline targets and kills leukemia cells and leukemic stem cells. The company also appointed him to its scientific advisory board.

"We wish to congratulate Aaron for again having his world class research recognized with a national award," commented SCT Chief Executive Officer, Dr. Niclas Stiernholm. "This recognition is well deserved and we feel very fortunate to be associated with him and his exciting cancer stem cell research."

About Dr. Aaron Schimmer:

Dr. Schimmer is a staff physician in the department of Hematology/Oncology at Princess Margaret Cancer Centre, a senior scientist at Ontario Cancer Institute and the head of Experimental Hematology at the University of Toronto. Dr. Schimmer is developing novel therapeutics for the treatment of acute leukemia. He is a strong proponent of 'drug recycling' where off-patent drugs are screened and tested to see what effects they have on cancer targets. This approach to drug development can be successful and highly efficient, as the toxicity and side effects related to the use of the drug in humans is already documented and well-understood. Dr. Schimmer is the author of over 135 papers, and has over 20 patents and patent applications. He has advanced three drugs with novel mechanisms of action from his lab into clinical trials for patients with acute leukemia. He has received over 30 awards and honours for academic achievement including an award from the Ontario Ministry of Research and Innovation for the best young scientists. In 2007, he was named one of Canada's Top 40 Under 40. Dr. Schimmer received the 2012 Till & McCulloch Award, presented each year by the Stem Cell Network in recognition of the year's most influential peer-reviewed article by a researcher in Canada.

About Stem Cell Therapeutics:

Stem Cell Therapeutics Corp. (SCT), a Toronto-based biopharmaceutical company, is Canada's only public company dedicated to advancing cancer stem cell discoveries into novel and innovative cancer therapies. Building on over half a century of leading and groundbreaking Canadian stem cell research, the company is supported by established links to a group of Toronto academic research institutes and cancer treatment centers, representing one of the world's most acclaimed cancer research hubs. SCT's clinical stage programs include the recently in-licensed tigecycline program, which is currently being evaluated in a multi-centre Phase I study in patients with Acute Myeloid Leukemia (AML), as well as TTI-1612, a non-stem cell asset being tested in a 28-patient Phase I trial in interstitial cystitis ("IC") patients, which is near completion. The Company also has two premier preclinical programs, SIRPaFc and a CD200 monoclonal antibody (mAb), which target two key immunoregulatory pathways that tumor cells exploit to evade the host immune system. SIRPaFc is an antibody-like fusion protein that blocks the activity of CD47, a molecule that is upregulated on cancer stem cells in AML and several other tumors. The CD200 mAb is a fully human monoclonal antibody that blocks the activity of CD200, an immunosuppressive molecule that is overexpressed by many hematopoietic and solid tumors. For more information, visit: http://www.stemcellthera.com

Caution Regarding Forward-Looking Information:

This press release may contain forward-looking statements, which reflect SCT's current expectation regarding future events. These forward-looking statements involve risks and uncertainties that may cause actual results, events or developments to be materially different from any future results, events or developments expressed or implied by such forward-looking statements. Such factors include changing market conditions; the successful and timely completion of pre-clinical and clinical studies; the establishment of corporate alliances; the impact of competitive products and pricing; new product development risks; uncertainties related to the regulatory approval process or the ability to obtain drug product in sufficient quantity or at standards acceptable to health regulatory authorities to complete clinical trials or to meet commercial demand; and other risks detailed from time to time in SCT's ongoing quarterly and annual reporting. Except as required by applicable securities laws, SCT undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

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Stem Cell Therapeutics' Clinical Advisor and Collaborator Receives Prestigious National Award