Stem Cell Research

Similarities Between Salamander Limb Regeneration And Stem Cell Repairs Of Damaged Human Muscle?

It turns out that the genes that make muscle stem cells in the embryo are surprisingly not needed in adult muscle stem cells to regenerate muscles after injury, a result that seems to relate to a parallel finding in salamander limb regeneration.

“The paired-box genes, Pax3 and Pax7 are involved in the development of the skeletal muscles," explained lead researcher Christoph Lepper, a predoctoral fellow at Carnegie Institution for Science’s Department of Embryology. "It is well established that both genes are needed to produce muscle stem cells in the embryo. A previous student, Alice Chen, studied how these genes are turned on in embryonic muscle stem cells. I thought that if they are so important in the embryo, they must be important for adult muscle stem cells. Using genetic tricks, I was able to suppress both genes in adult muscle stem cells. I was totally surprised to find that the muscle stem cells are normal without them.”

Perhaps coincidentally, perhaps not, the Carnegie finding brings to mind a recent research result from the Max Planck Institute regarding salamanders.  Salamanders regrow lost limbs and Elly Tanaka at Planck has been studying how they do so. Tanaka and colleagues found that salamander regeneration begins when a clump of cells called a blastema forms at the tip of a lost limb. From the blastema come skin, muscle, bone, blood vessels and neurons, ultimately growing into a limb virtually identical to the old one.

But here's the surprise: Rather than having their cellular clocks fully reset and reverting to an embryonic state, cells in the salamanders’ stumps became slightly less mature versions of the cells they’d been before.  In other words they don't revert to pluripotency.

Company Founded By James Thomson Reprograms Blood Cells into Stem Cells

Cellular Dynamics international (CDI), founded by Jamie Thomson and colleagues from the U. of Wisconsin, recently reported generating pluripotent stem cells from very small volumes of ordinary human blood samples. CDI is privately held.  Its stated mission is to "provide drug screening and toxicity testing products based on breakthrough induced pluripotent stem (iPS) cell technology,"

Once the difficulty of current approaches to inducing pluripotency is overcome (reducing time and cost while producing high quality scalability and safety), this development suggests the possibility of a readily obtainable source of pluripotent stem cells from the millions of blood samples in storage at repositories and healthcare institutions worldwide.

New Cedars-Sinai Regenerative Medicine Institute to Emphasize Induced Pluripotent Research

The Cedars Institute will be housed in new state-of-the-art laboratories being constructed especially for stem cell and regenerative medicine research. At the heart of the Institute will be a specialized core facility for the production of Induced pluripotent stem cells.

Clive N. Svendsen, Jamie Thomson associate and joint leader of the widely-respected Stem Cell and Regenerative Medicine Center at the University of Wisconsin, has been named to lead the new unit.  He has quite a resume; one that includes professor of neurology and anatomy at the University of Wisconsin-Madison, and consulting professor at Stanford University. Svendsen’s research focuses on both modeling and treating neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and Parkinson’s disease using a combination of stem cells and growth factors.

NIH Stem Cell Rules Seriously Flawed, Says Stanford Expert

On Monday the National Institutes of Health released their final guidelines detailing what types of human embryonic stem cell research will qualify for federal funding. Although the rules permit federal funding of research on embryonic stem cell lines produced from excess early embryos from in vitro fertilization clinics, they disallow federal support of two key techniques used to derive embryonic stem cells in animals: that of transferring the genetic material from one cell into an egg without a nucleus, and that of stimulating an unfertilized egg to divide.

"In terms of extending the classical embryonic stem cell lines that can be used with federal funding, this is an important step forward," said Stanford University School of Medicine stem cell researcher Irving Weissman, MD. "However, the policy banning funding of other stem cell lines produced by transferring the genetic material from a patient to an egg is a terrible disappointment. It seems inconsistent with the president's promise to allow scientific facts to determine science policy." On March 9, President Barack Obama made a statement about his administration’s approach to science policy, in which he vowed to ensure "that scientific data is never distorted or concealed to serve a political agenda, and that we make scientific decisions based on facts, not ideology."

June 2009's Stem Cell Sector Stock Price Winners and Losers

As noted in May, we've begun adding a comparison of individual company stock price with the prior month and have included the percentage change in individual prices from the end of the previous month to the end of the latest one. Sector Companies are then ranked by percentage stock price change, highest to lowest, in a downloadable PDF file. You'll find the file following the list of percentage winners and losers.

June's largest percentage stock price increases among our 21 company Stem Cell Sector were:

1. Advanced Cell Technology (ACTC.PK) - 63%
2. Aastrom Biosciences (ASTM) - 24%
3. Thermogenesis Corp. (KOOL) - 19%

May's largest percentage stock price decreases in our 21 company Stem Cell Sector were:

1. Medistem Laboratories (MEDS.PK) - (-22%)
2. International Stem Cell Corp. (ISCO.OB) - (-14%)
3. Neostem Inc. (NBS) - (-11%)

Comparative 21 Company Stem Cell Sector chart June 30 vs. May 31, 2009:

• Sector Individual Market Values EOM 6-09 vs 5-09

The sector as a whole increased in value by 11% during June.  Comparatively, the nasdaq composite increased 3.4%.

• Sector Selected Market Value by Month 6-09

Blood Stem Cell Growth Factor Found to Reverse Memory Decline in Mice

A human growth factor that stimulates blood stem cells to proliferate in the bone marrow reverses memory impairment in mice genetically altered to develop Alzheimer's disease, researchers at the University of South Florida have found. The granulocyte-colony stimulating factor (GCSF) significantly reduced levels of the brain-clogging protein beta amyloid deposited in excess in the brains of the Alzheimer's mice, increased the production of new neurons and promoted nerve cell connections.

GCSF is a blood stem cell growth factor or hormone routinely administered to cancer patients whose blood stem cells and white blood cells have been depleted following chemotherapy or radiation. GCSF stimulates the bone marrow to produce more white blood cells needed to fight infection. It is also used to boost the numbers of stem cells circulating in the blood of donors before the cells are harvested for bone marrow transplants. Advanced clinical trials are now investigating the effectiveness of GCSF to treat stroke, and the compound was safe and well tolerated in early clinical studies of ischemic stroke patients.

"GCSF has been used and studied clinically for a long time, but we're the first group to apply it to Alzheimer's disease," said USF neuroscientist Juan Sanchez-Ramos, MD, PhD, the study's lead author. "This growth factor could potentially provide a powerful new therapy for Alzheimer's disease – one that may actually reverse disease, not just alleviate symptoms like currently available drugs."

Differences Found Between Induced Pluripotent Stem Cells And Embryonic Stem Cells

One of the arguments for federal funding of embryonic stem cells -- in light of the progress being made in Induced Pluripotent Stem Cell technology -- is pretty straight forward.  Researchers have used 'embryonic-like' to describe the result of induced regression on adult cells, usually skin cells. The reason embryonic-like is used is that we have not been sure whether they were identical to embryonic stem cells.  In fact, we don't know enough about how embryonic stem cells become every cell in the body to know exactly what 'embryonic-like' means.

In another example of the kind of end run occasionally taking place in the rapidly expanding stem cell research arena, UCLA researchers have found that embryonic stem cells and skin cells reprogrammed into embryonic-like cells have inherent molecular differences, demonstrating for the first time that the two cell types are clearly distinguishable from one another.

Pluristem Therapeutics Awarded $1.9 Million Grant from Israeli Government

Grants have become a major source of short term funding for many of our Sector Companies in recent months.  The latest is Pluristem Therapeutics (PSTI) about which we posted recently.  The company uses placental stem cells expanded in a proprietary bioreactor to address several diseases. 

Pluristem has been awarded a $1.9 million government grant from the Office of the Chief Scientist (OCS) at the Ministry of Industry, Trade and Labor of Israel, as a government participation in R&D expenses for the period March 2009 to February 2010. The OCS awards grants to industry in Israel to foster technological innovations. This is the fourth consecutive year that Pluristem has received this respected grant. The funds will be designated and used by Pluristem to support the clinical trials of the allogeneic placental-derived adherent stromal cell product, termed PLX-PAD, for the treatment of critical limb ischemia (CLI), the end-stage of peripheral artery disease (PAD), as well as for other research and development activities of the Company.

Adapted from the Pluristem Therapeutics announcement.

Athersys To Receive Grant Funds From Ohio's Research Commercialization Program

Following California's lead, and in response to growing acceptance of the benefits of regenerative medicine given sufficient research, more and more states are finding ways to fund research taking place within their borders.

The Center for Stem Cell & Regenerative Medicine (CSCRM), comprised of Case Western Reserve University (CWRU), Cleveland Clinic (CC), University Hospitals (UH), and Athersys, Inc. (ATHX - a Sector Company) has received 5 million dollars from Ohio's Third Frontier Commission under the Research Commercialization Program. The funding will help support new and innovative stem cell technologies including two commercial, four emerging and three pilot projects. This funding will be matched by each of the projects to create a $10 million grant benefiting stem cell and regenerative medicine in Ohio.

Medicine's New Toolbox: MIT's View Of Induced Pluripotency's Future

"The past two years have been nothing short of a revolution," says John Dimos, a senior scientist at iZumi Bio. "These cells didn't really exist two years ago. This is all brand-new technology, and it's opening up the potential for brand-new science." The company John is with, Izumi Bio, plans to take advantage of that potential by developing a bank of iPS cells from patients with various diseases and using the cells to screen candidates for drug development.

As a postdoc at Harvard, John Dimos built a cellular model of ALS (amyotrophic lateral sclerosis - Lou Gherig's Disease), making it possible to study a neurodegenerative disease outside an animal for the first time. He and his colleagues collected skin cells from an 82-year-old woman with ALS, reprogrammed them into iPS cells, and directed the cells to differentiate into motor neurons that were genetically identical to the donor's defective cells. "It was the first paper to show that you can use a stem cell to see disease pathology in a petri dish," says Douglas Melton, codirector of the Harvard Stem Cell Institute. "That means you can now study diseases in petri dishes and not in people. That's huge."

Pluristem Therapeutics Receives European Regulatory Approval for Placental-Derived Stem Cell Clinical Trial

A recent study by Children's Hospital Oakland suggests the placenta contains the same quality stem cells as cord blood but in much larger numbers.  The primary problem with cord blood has been the relatively small harvest of stem cells for use in transplants. 

Pluristem Therapeutics, one of our Sector Companies, specializes in therapies derived using placental derived stem cells.  Now, the European Union, has approved the Company’s Clinical Trial Application (CTA) and granted approval to begin clinical trials with its placental-derived adherent stromal cell product, termed PLX-PAD, for the treatment of critical limb ischemia (CLI), the end-stage of peripheral artery disease (PAD). In addition, Pluristem has already received approval from the Ethics Committee and, as previously announced, the US Food & Drug Administration (FDA) had cleared the Company’s Investigational New Drug (IND) application to initiate a similar trial in the United States. Both approvals of the CTA and IND clear the way for the world’s “first-in-man” clinical trial using PLX-PAD.

Pluristem’s placental-derived stem cells are expanded using the company’s proprietary 3D PluriX™ technology. PLX-PAD is an off-the-shelf, one-size-fits-all product that needs no tissue matching prior to being administered to patients. In these phase I trials, to be conducted at multiple locations in the US and Germany, PLX-PAD will be administered to patients considered "late stage" that have not responded to traditional medical or surgical interventions.

In the US alone, it is estimated that 8-12 million people suffer from critical limb ischemia associated with PAD. Several Sector Companies are researching and testing applications for critical limb ischemia.

Adapted from the Pluristem Therapeutics announcement.

Cytori Therapeutics Vs. Thermogenesis: A Fascinating Difference In Market Values

There are many reasons companies entering the commercialization stage of product  development might be valued differently by the stock market.  Some of them are rational, others are not. Thermogenesis (KOOL) and Cytori (CYTX) provide a great case study in market capitalilzation. While the companies are very similar in many ways, the market sees them as substantially different from one another.

Thermogenesis has arguably been a 'commercialization stage' company for almost ten years while Cytori is still arguably not in the commercialization stage even now although it has begun book sales. To some extent the market views Thermogenesis as a mature but unprofitable player in the cord blood processing and storage market and nothing more.  Relative to Cytori, which has yet to prove it has a broad commercial market, this perception of unprofitable maturity has hurt Thermogenesis.

Looking only at revenues, KOOL's were $21.9 million in its last fiscal year and $5.1 million in the March quarter; CYTX revenues were $4.5 million in its last fiscal and $1.9 million for the March quarter.  KOOL had a market value on Monday, June 15, of $41 million while CYTX's market value drifted down to $129 million from $138 million in Friday's trading session. Like KOOL, CYTX continues to lose money. In terms of cash burn, Cytori has less than a year's cash remaining while Thermogenesis projects profitability on a continuing cash basis within the next few operating quarters.