Next-Generation Cell Therapy for Graft-Versus-Host Disease

Endonovo Therapeutics, Inc has announced its development of a cell-based treatment for Graft-versus-Host Disease (GvHD). This treatment utilizes umbilical cord blood stem cells that have been grown and enhanced by specific treatments.

GVHD occurs when newly transplanted donor cells attack the recipient’s body. It can occur after a bone marrow or stem cell transplant if the cells have not been properly matched or even if the donor and recipient are relatively well matched. The chances of suffering GVHD are around 30 – 40% if the donor and recipient are genetically related and close to 60 – 80% when the donor and recipient are not related.

GVHD can be either acute or chronic and the symptoms of GvHD can be either mild or severe. Typically, acute GVHD comes on within the first 6 months after a transplant. Common acute symptoms include: Abdominal pain or cramps, nausea, vomiting, and diarrhea, Jaundice (yellow coloring of the skin or eyes) or other liver problems, skin rash, itching, redness on areas of the skin. Chronic GVHD usually starts more than 3 months after a transplant, and can last for the lifetime or the patient. The symptoms of chronic GvHD include: dry eyes or vision changes, dry mouth, white patches inside the mouth, and sensitivity to spicy foods, fatigue, muscle weakness, and chronic pain, joint pain or stiffness, skin rash with raised, discolored areas, as well as skin tightening or thickening, shortness of breath, weight loss.

Endonovo uses a novel method to enhance stem cells. Their so-called “Cytotronics platform” utilizes Time-Varying Electromagnetic Field (TVEMF) technology to expand and enhance the therapeutic properties of stem cells and other types of cells for regenerative treatments and tissue engineering. This platform can potentially optimize cell-based therapies so that they have greater therapeutic potential than they had prior to their treatment.

The Cytotronics™ platform dates back to experiments conducted at NASA to expand stem cells in culture. NASA’s goal was to create stem cell therapies that could be used to treat astronauts during long-term space exploration. NASA scientists showed that Time-Varying Electromagnetic Fields (TVEMF) could stimulate the expansion of stem cells in the lab. Additionally, TVEMF increased the expression of dozens of genes related to cell growth, tumor suppression, cell adhesion and extracellular matrix production.

By testing and tweaking this technology over a period of 15 years, Endonovo scientists created a novel protocol for augmenting the therapeutic properties of cells in culture through physics rather than genetic engineering. The Cytotronics™ platform seems to be able to make stem cells that express higher levels of key genes necessary for tissue healing and regeneration.

As an example of the efficacy of this technology. Endonovo scientists have shown that Cytotronic™ expansion of peripheral blood stem cells resulted in an over 80-fold expansion of CD34+ cells in as little as 6 days.

Endonovo is using the Cytotronic platform to enhance the regenerative properties of mesenchymal stem cells (MSCs), which have the capacity to staunch inflammation in patients with GvHD and other inflammatory diseases.

However, despite their promise, MSC-based therapies suffer from poor engraftment and short-term survival when transplanted into sick patients. These remain major limitations to the effective therapeutic use of MSCs. If there was a safe and effective way to beef up the survival and regenerative properties of MSCs, such a technique would be indispensable.  This makes MSCs prime candidates for the Cytotronic Platform.

Dr. Donnie Rudd, Chief Scientist & Director of Intellectual Property at Endonovo, said: “Our Cytotronics platform is particularly suited to address many of the issues that have plagued stem cell therapies that have recently failed, such as their loss of potency and self-renewal when expanded ex vivo, their poor engraftment and their limited ability to survive when transplanted.”

Earlier this year, Endonovo announced a protocol for the creation of a cell mixture from a portion of the human umbilical cord co-cultured with adipose-derived stem cells. This resulting cell mixture contains a rich source of highly-proliferative, immunosuppressive cells that are not recognized by the patients immune system, since they contain neither of the major histocompatibility markers (HLA double negative). These cells are “immune privileged,” which means that are not recognized as foreign cells by the patient’s immune system, and therefore are a significant source of cells for MSC-based therapies.

Endonovo Therapeutics has used this new technology to create a biologically potent, off-the-shelf, allogeneic treatment for Graft-Versus-Host disease and a wide-array of other conditions. They would like to test these products in clinical trials eventually.

Endonovo hopes that stem cells enhanced by the Cytotronics™ platform will become a major innovation in the regenerative medicine market.

“We are very excited to be a leader in the development of next-generation, ex vivo enhanced cells for regenerative medicine,” stated Endonovo CEO, Alan Collier. “We have seen several stem cell therapies fail in clinical trials over the last couple of years, which points to a critical need for the development of methods to increase the biological and therapeutic properties of stem cells.”

“We believe that enhancing the biological and therapeutic properties of stem cells using bioelectronics is the future of cell-based therapies,” concluded Mr. Collier.

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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).