Applied BioLogics

The public and scientific perception is that only embryonic stem cells are pluripotent.  The definition of pluripotent means the stem cell can become any other cell in the body.  As babies we are all formed from our own embryonic stem cells.  Embryonic stem cells are truly pluripotent. But embryonic stem cells also carry individual DNA. If you implant the embryonic stem cell into a person who is not a genetic match, the host immune system will reject the stem cell or the tissue it tries to become.  The second side effect is for the transplanted embryonic stem cell to grow in a wild and rapidly dividing fashion similar to cancer and produce tumors.  This is a big stumbling block for the therapeutic application of embryonic stem cells.  Pharmaceutical companies are trying to develop anti-rejection drugs to use in conjunction with embryonic stem cells and other genetic based drugs to control the differentiation process of cell growth.  It is a very large and expensive hurdle to overcome.

The Koreans are trying to get around this issue by transferring the patients DNA into the test tube embryo, hence cloning the embryonic stem cells to be a genetic match. The cloned embryonic stem cell can then be used in therapy on the patient without fear of rejection.  They call it therapeutic cloning.  There are two ethical questions.  One is the growing of the embryo to be sacrificed to harvest stem cells.  Most of the religions and spiritual faiths of the world consider life to begin at conception and therefore the embryo represents a life.  What else can the human embryo become other then a human child.  The embryo is destroyed when the stem cells are harvested.  The second is the cloning research aspects.  The cloned embryo could be just as easily implanted in a womb and a cloned baby delivered.  A lot of cloning research can be hidden in embryonic stem cell research.  The Stowe Foundation believes the public is entitled to know the complete picture.

The early work with adult stem cells, stem cells found in the adult bone marrow and other tissues of the body, showed that the cells being derived from the bone marrow were actually progenitor cells.  The progenitor stem cells could only become very specific cell lines.  Adult stem cells were not pluripotent; they were at best progenitor cells.  This became the conventional wisdom. You would have to find a progenitor cell line for each organ of the body.  The progenitor stem cells also had to be activated to differentiate or turn into a specific cell line.  Activation was different for each organ.  Plus, progenitor cells were limited in number and they would have to be expanded or reproduced in a cell culture to get a therapeutic dose.

Hence the leading research scientists of the time felt that embryonic stem cells held much higher promise as therapeutic agents.  It is a biological fact that embryonic stem cells are pluripotent and therefore nearly all research scientists turned to embryonic stem cells.  The most available supply of embryonic stem cells was to harvest them from fetuses aborted in the first five weeks of pregnancy. The second supply was to grow an embryo in a test tube and harvest the stem cells and sacrifice the embryo.  So as embryonic stem cell research grew, so did the ethical controversy.

The abortion stigma and growing an embryo to be sacrificed are major ethical hurdles for embryonic stem cell research in the United States.  In addition, the immune rejection problem has not been solved.  The animal studies show the embryonic stem cells that are not genetically matched sometimes grow tumors instead of new organ tissue.  All positive clinical studies on humans have been done with adult stem cells.  Still the vast majority of research dollars flows to embryonic stem cells because of the pluripotent image.

The Stowe Foundation can change this dynamic.  We have discovered what appears to be a pluripotent adult stem cell in the bone marrow.  This is the stem cell that produces all of the progenitor cells that were used in the original adult stem cell work.  The pluripotent adult stem cells can become any other tissue in the body.  We are in the process of characterizing these stem cells and developing a harvesting technique specific to these stem cells, which we call UPS, Universal Pluripotent Stem Cells.  We are also working on a technique to rapidly reproduce these pluripotent adult stem cells so we can transplant a large number of UPS cells into a damaged organ to regenerate a new organ or restore function.  In addition, the bone marrow is the source of a bone marrow concentrate (BMC) which contains not only the UPS cell, but also all of the co-factors such as colony stimulating growth factors, to assist the UPS cell in tissue repair and regeneration.

The FDA considers the expansion and the purification of the UPS cells to be the same as creating a new blood product, so we have to do the clinical studies in two steps.  First we have to harvest the bone marrow concentrate containing the UPS cells and immediately transplant the unaltered adult stem cells from the bone marrow into the heart.  The FDA has ruled the BMC to be an autologous blood product, which means the BMC can be used in any therapeutic application in which the BMC has been proven to be safe and effective.  Harvest Technology out of Boston, MA has obtained FDA clearance for the use of the BMC in orthopedic applications.  The Spanish and Germans have been transplanting a mixture of bone marrow concentrates into the heart for several years with good results.  Significant improvement has been documented in contractility of the heart muscle and ejection fraction.  Doctors in South America have been investigating the bone marrow derived stem cells in the care of diabetics    The Foundation has been to both European transplant centers and the South American facilities to receive training in the surgical procedures and to review the data on their results.

Our technique of harvesting the bone marrow yields significantly greater number of the targeted UPS stem cells then either the German or Spanish procedure, so we expect to generate even better results.   We are completing all of the large animal studies to prove safety and efficacy on the test protocol and we have scheduled a phase I human trial in Mexico.  The phase I human study will be to FDA standards. The Stowe Foundation will also incorporate an arm of the study that uses the immune therapy protocols of Applied BioLogics to improve results.

Our first goal is to treat chronic heart failure.  The target patients are those who had a myocardial infarction six months to ten years ago and are now looking at a weak heart performance.   We will transplant the UPS cells into the heart and evaluate the functional improvement of the heart.   A certain percentage of these patients will not qualify for the transplant procedure because their arteries are clogged with plaque.  This makes it impossible to insert the catheter used for the infusion of the UPS cells.  Those patients who are excluded from the study will be put on an experimental plaque treatment program and transplanted six months later, if the arteries are sufficiently opened.  A third cohort of transplanted patients will be put on an immune support program to help the stem cells heal the heart.

Large animal studies will be performed on the lungs, pancreas, liver and brain while the phase I heart study is being conducted.  This will allow the UPS cell therapy to be expanded to include emphysema, diabetes, cirrhosis, and stroke.  In addition, the UPS cells will be expanded on a number of healthy bone marrow donors to verify to the FDA that no endotoxins are introduced during the procedure and that the UPS cells are not altered in any way by the expansion step.  The same expansion step will then be done on dog bone marrow and the expanded UPS cells infused into the heart.  This will prove the safety of the procedure. The next step would be to look at the efficacy of the transplant on heart failure by using dogs with an induced myocardial infarction.  In essence, we repeat the dog studies with the expanded UPS cells and then we repeat and duplicate the phase I human study.  At the end of the phase I studies, the Foundation will have the only comprehensive immune therapy protocol for four of the most devastating chronic illnesses; heart disease, stroke, diabetes and liver cirrhosis.

This will create a demand for the UPS cells in other conditions such as knee and joint repair, spinal cord injuries, wound and ulcer repair, tendon and ligament surgery.  All varieties of cosmetic surgery will benefit from the healing powers of the UPS cells.  The Foundation will work closely with our IP firm to decide which technologies should be patent protected and which are best kept as a trade secret.  At some point, the technology will be brought to the United States for the phase II studies.  The Foundation will then license the technology for commercial development.  That will provide a revenue stream for the Foundation to continue its work.