Applied BioLogics

Osiris and other adult stem competitors to the Stowe Foundation technology platform are using what the industry calls a purified adult stem cell line. They are generally focused on calling the CD34 cell or the mesenchymal cell a "stem cell".  It is really a progenitor cell and can only further differentiate into a couple of cell lines, one of which is muscle, so the Germans use it in their heart studies.  Bone is another cell line that can be formed from CD34 cells.  You have to match your tissue repair to the progenitor cell you are trying to use. Progenitor cells are found throughout the body, so you can harvest them from many different areas of the body. You look for a rich source of the progenitor cells in the blood, the fat tissue of the central nervous system, the epithelial layer of the skin and the bone marrow.

Many techniques exist for recovering the “stem cells”. The most common is to aspirate the bone marrow or use electrophoresis on the peripheral blood and get a broad mixture of cells. They take the mixture into a molecular biology lab and filter the blood product or bone marrow aspirate in a process called the Ficoll gradient technique.  The Ficoll gradient produces a very pure strain of CD34 cells.  The final number of CD34 cells is not near the number as was in the original mixture as a significant number of the cells are lost to the separation process. But, a pure cell culture is obtained and this is thought necessary to study stem cell therapy. The Ficoll gradient technique takes several hours and is done outside of the surgical suite.  So chain of command protocols have to be installed.  It is not point of care service.

Once the CD34 cells are processed through the Ficoll technique you do not have enough "stem cells" to have a therapeutic dose.  Hence you force the CD34 cells that you have collected to reproduce.  You expand the number of “stem cells” to get a therapeutic dose.  Every company has their own proprietary techniques for the expansion step. This is where the FDA gets involved.  You have to demonstrate that your expansion technology is not inadvertently changing the cells.

Genetic mutations are known to occur during the rapid cell divisions that take place during the expansion step.  The cells are being more then minimally altered.  According to the FDA, that means you are creating a new blood product and the lab where you do the expansion step has to meet certain standards and the process itself has to meet certain standards.  For example, you have to prove that you do not introduce an endotoxin in the process due to your growth medium.  You are in fact creating a new blood product.  The entire process takes 3 to 4 days.

Hence the patient has to wait to get the therapeutic dose of stem cells back from the lab.. And remember, this is a pure cell line.  There are no growth factors, there are no cytokines, and there are no mononuclear cells in this pure cell line.  Also they erroneously call the CD34 cell a stem cell.  They are progenitor cells and they are injected or infused without the co-factors that control the differentiation process and control the repair process.

This is what they have learned from their animal and clinical studies. What they are calling stem cells are really progenitor cells.  Pure progenitor cells, no matter how many you use, need help. They are now looking at trying to find the right cocktail of growth factors and cytokines to co-infuse with their purified cell line.  They are also trying to match their progenitor cells to some type of therapeutic benefit. They have a much greater FDA hurdle to cross and they really do not understand how the human immune system works to regenerate tissue.  They will chase their tails forever trying to come up with a therapeutic application and the correct cocktail of co-factors.

The Stowe Foundation working with Harvest Technology has created an entirely different approach. First we recognize that the bone marrow produces a truly pluripotent adult stem cell.  We call it the UPS cell, the Universal Pluripotent Stem Cell.  It is our trade secret.  It is not the CD34 cell or any of the progenitor cells.  The pluripotent adult stem cell is the precursor to the progenitor cells. The Ficoll gradient technique throws it out during the purification process.  The UPS cell is very small in size.  It has been ignored in stem cell research because early on conventional wisdom ruled that only the embryonic stem cell could be pluripotent.  That is a false conclusion.  The Stowe Foundation is supporting Dr. Ewa Carrier at the University of California San Diego (UCSD) in her attempt to identify and characterize the UPS cell.

It is a very small molecule and even the research associates at The Stowe Foundation have not been able to create a suitable purification technique to harvest just the pluripotent adult stem cell.  A harvesting technique will ultimately be required to fully study the cell. But even the UPS cell needs all of the co-factors to differentiate into the tissue that needs to be repaired.  So we just leave it in the bone marrow concentrate (BMC) and study the therapeutic benefits of the BMC.

The FDA has approved the Harvest Tech equipment to produce an autologous blood product for cell therapy. So the bone marrow concentrate can be used in any application where human cell therapy is approved for therapeutic use. In the US that happens to be orthopedics.

This is how the Harvest Technology device works as a source of stem cells.  You aspirate 60 cc of bone marrow, 10cc at a time. You place the bone marrow aspirate into the Harvest Technology equipment and centrifuge for 20 minutes. The bone marrow aspirate will separate into three phases. One of the phases is the bone marrow concentrate.  It is a true autologous blood product. It will in fact contain a large population of CD34 cells and other progenitor cells and it will contain all of the co-factors.  It also contains the UPS cell.

The Stowe Foundation did all of the large animal studies to demonstrate that the BMC can be safely injected into a wide variety of organs.  Hence we are prepared to move into the human clinical studies on the therapeutic applications of the BMC. Harvest Technology simply provides the device. We are already legal for orthopedics in the US and will be legal in Mexico for a wide variety of applications upon completion of the clinical trials.

At Cornell University we conclusively showed that the BMC can grow new cartilage.  The BMC can be just as easily be used in human orthopedic applications and it has been used throughout Europe and a few times in the US.  The FDA has ruled the BMC to be an autologous blood product suitable for clinical applications.  However, we have to still create the clinical applications by demonstrating the therapeutic benefits.  Fortunately, orthopedics is already approved by the FDA for human cell therapy.

One example in cartilage repair is Autologous Chondrocyte Implants (ACI).  The cartilage repair surgery uses chondrocytes as progenitor cells.  The chondrocytes have to be harvested from healthy cartilage before being transferred to the damaged area.  So repairing a knee with current cell therapy is a three step process. First you have to take cartilage from a healthy area, then you treat the cartilage to recover chondrocytes, then you surgically implant the chondrocytes into the damaged area.  You can only do this with a traumatic knee injury.  It does not work with arthritis.

The inflammation associated with arthritis simply destroys the chondrocytes.  The Stowe Foundation can eliminate the chronic inflammation using immune therapy. Hence our stem cell therapy techniques combined with immune therapy brings us one step closer to a cure for arthritis.  Human cell therapy with autologous blood products is already FDA certified in orthopedic applications and Stowe BioTherapy has opened a clinic fully equipped to handle chronic inflammation.  We simply use an orthopedic surgeon to transplant the BMC to the correct location.

The Stowe Foundation has set up the clinical studies in Mexico that will allow us to apply the BMC to repair the heart. Other organizations have gotten good results with purified progenitor cells with heart patients. But they do not address the underlying chronic inflammation associated with heart disease.  The Stowe Foundation believes that the stem cells, used as a stand alone therapy will be a temporary band-aid.  Just like many by-pass operations have to be repeated, the stem cell procedures of today will need to be repeated.  Again it is because the medical community has not been trained to reverse chronic inflammation and stop the disease process.

There is no magic bullet to chronic inflammation. Chronic inflammation comes from the PITTS- Syndrome. It takes Applied BioLogics to reverse the PITTS-Syndrome.  Both Applied BioLogics and The PITTS Syndrome are concepts created by The Stowe Foundation to treat and reverse chronic inflammation. You can then apply the BMC to repair the damaged tissue. It is not a hard concept to appreciate, but it defies the pharmaceutical and bio-tech model of medicine.  That means it confuses Wall Street and all of their life science analysis. It is however the way the body works.  Recognizing the regulatory hurdles that have to be crossed, The Stowe Foundation is looking for academic partners that would be willing to clinically test the BMC.  That is the first step towards ultimate FDA approval.