Blood-forming stem cells in adult humans produce billions of red and white cells each day and are critical components of bone marrow transplantation procedures used in the treatment of some cancers and blood cell deficiencies. Amy Wagers at the Harvard Stem Cell Institute adds that for patients undergoing bone marrow transplant, the success of the procedure requires (1) collection of sufficient numbers of stem cells for transplant, (2) efficient migration of these cells after transplant to their proper locations within the bone marrow, and (3) proliferation of these cells in the body to rapidly reproduce mature red and white blood cells. Inefficiency at any of these steps can limit patient access to transplant or result in transplant failure.
Several of our Stem Cell Sector companies produce scalable stem cell mixtures combined with growth factors. Athersys and Osiris, to cite two examples, have scalable stem cell products. We note these two products because they are examples of hoped for off-the-shelf mesenchymal stem cell therapies in which major pharma has taken an interest. Athersys recently entered a development agreement with Pfizer for Multistem. Osiris sold foreign commercialization rights for Prochymal to Genzyme in late 2008..
Athersys Inc.'s product is called Multistem which the company describes partially as follows:
MultiStem is a patented and proprietary cell therapy product consisting of a special class of stem cells that are obtained from the bone marrow of healthy, consenting adult donors, and which have the demonstrated ability to produce a range of factors, as well as form multiple cell types. MultiStem appears to promote tissue repair and healing through the production of multiple therapeutic factors produced in response to signals of inflammation and tissue damage.
Multistem exhibits each of the following characteristics based on research and development to date: (1) it may be produced on an industrial scale, in a well validated and reproducible manner; (2) it may be administered without tissue matching or the need for immune suppressive drugs, making it analogous to type O blood; (3) it exhibits a consistent safety profile; and (4) it appears capable of delivering a therapeutic benefit through more than one mechanism of action. Factors expressed by MultiStem are believed to reduce inflammation and regulate immune system function, protect damaged or injured cells and tissue, promote formation of new blood vessels, and augment tissue repair and healing in other ways.
Here is what Osiris Therapeutics says about its stem cell therapeutic product: Prochymal:
Prochymal is a highly purified formulation of mesenchymal stem cells (MSCs) that are grown in culture, permitting large-scale production. The MSCs utilized in Prochymal(TM) are isolated from the bone marrow of healthy adult donors. Because the cells can be expanded, thousands of doses can be produced from a single donation. Numerous studies have demonstrated that the stem cells in Prochymal(TM) are able to safely facilitate tissue repair through a number of mechanisms. Specifically, MSCs are able to down-regulate severe inflammation.
It is easy to see how similar these products appear to be. While Athersys doesn't specifically say so, the source and characteristics they provide for Multistem suggests it also consists primarily of mesenchymal stem cells. We note that there has been limited success only, so far, in clinical trials for GVhD and Chron's Disease with Osiris' Prochymal. In both cases prohymal was intravenously administered. Both Athersys' Multistem and Osiris' Prochymal are also being tested for Acute Myocardial Infarction. In both cases the stem cell therapy is intravenously administered.
To review Amy Wagers summary above, in order to be therapeutically effective stem cell therapies must accomplish three things: (1) collection of sufficient numbers of stem cells for transplant, (2) efficient migration of these cells after transplant to their proper locations within the bone marrow, and (3) proliferation of these cells in the body to rapidly reproduce mature red and white blood cells.
While Ms. Wagers was speaking of bone marrow transplants specifically, her summary of what stem cells must do can be expanded to any stem cell therapy. Both Athersys and Osiris have solved number one, at least apparently so. Number two seems to take place by some bodily indication communicated to the stem cells. That said, there are several ongoing studies that inject stem cells, for example, directly into the heart at the point of damage. This suggests that it isn't clear at this point which method of supplying the stem cells is superior. To the Wagers summary can be added that, (4) the stem cells must make only the cells required for regeneration (in other words, no tumor cells for example) and (5) the stem cells must stop creating regenerative tissue exactly at the point the job is done.
In the end, will allogeneic mesynchmal stem cells administered in yet undetermined fashion -- perhaps in certain applications by utilizing some bioactive nanomaterial -- provide a general solution to a wide variety of diseases? Or will certain autologously determined stem cell therapies be better suited for a variety of applications?
At this point we have one medical equipment manufacturer in the Stem Cell Sector that has created a $275 million dollar market capitalization by convincing investors it has a machine that will extract autologous stem cells from fat tissue in a way more therapeutic than the autologous stem cell extracting devices made by a number of other companies. That value places the company second only to Geron in Sector market capitalization, Cytori Therapeutics is currently a market darling because it has managed to associate itself with the developing field of stem cell based breast reconstruction, the effect of which is being studied by plastic surgeons in several countries.
We also have a company in the Sector, Neostem Inc., with a current market capitalization of $57 million, that is in the business, among others, of collecting and cryo-storing autologous adult stem cells for future use. This business seems to rely on the unproven belief that your stem cells at age 25 will somehow be superior therapeutically to your own adult stem cells at age 50. It also presupposes that the storage of adult stem cells will be worthwhile in terms of therapeutic efficiency relative to induced pluripotent stem cells or some other form of scalable stem cell product that has beaten the rejection problem.
It is not clear whether embryonic stem cell therapies, induced pluripotent stem cell therapies, or direct therapies consisting of scaled up numbers of specific organ stem cells will end up being the most therapeutic and the lowest relative cost. What is clear is that a number of companies and investors are betting on very different approaches to regenerative medicine and so far they're doing so based on very limited information.
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