Bone Marrow Mesenchymal Stem Cells to Heal Chronic Diabetic Wounds
Our goal was to engineer a device to improve healing in diabetic foot ulcers, a devastating consequence of diabetes that occurs in about 25% of all diabetic patients and is responsible for most leg or foot amputations. More than 3 million people in the US and up to 91 million people worldwide have diabetic foot ulcers (DFU). There is a clear medical need. There are products on the market that can improve wound healing for some, but not all patients. This causes a large financial burden for the health care system, and great suffering for the patients who live with open wounds, often infected, that progress to amputations. Therefore there is a clear medical need for advanced therapies to heal diabetic ulcers faster.
We proposed to create a device consisting of a scaffold for dermal regeneration (SDR) populated with mesenchymal stem cells (MSC) that have been pre-conditioned for optimized reparative function. We formed a team of established wound and stem cell/matrix experts, and this team has indeed successfully engineered and demonstrated efficacy of the device in two animal models, and is now ready to progress to IND-enabling studies in support of our very promising Development Candidate.
During this Early Translational grant, we developed a product that consists of an FDA-approved scaffold for dermal regeneration (SDR) filled with human bone marrow-derived Mesenchymal Stem Cells (MSC). These are then pre-incubated for 2 days in hypoxia and in the presence of a beta adrenergic antagonist. We have completed studies that demonstrate that this “next generation” stem cell product is highly efficacious in healing skin wounds, using diabetic mouse models.
In this third year of funding, our top priority was to evaluate our product in a pig model for skin wound healing. Confirming our previous results in diabetic mice, we found that two weeks after administrating our product to the wounds of a Yucatan minipig, we achieved over a 20% higher rate of wound healing (re-epithelialization) as compared to SDR alone. These results are very promising, even more so because the improvement we note is in normal, healthy pigs, who ordinarily heal well. We anticipate that when we use this device on wounds that are infected, or in diabetic animals, where healing is delayed or impaired, the increase in healing rates will be even greater.
We are very excited about these results and hope to continue working on this project through future CIRM funding, in order to bring this highly promising therapeutic to a clinical trial.