Houston Methodist Team Carves a NICHE in State-of-the-Art Diabetes Therapy

Grattoni and Nichols have a long history of successful collaboration and this new R01 award represents the culmination of many smaller successes along the way. The first organization to financially support this work was the Vivian Smith Foundation, which has been continuously funding it for nine years at $100,00 per year. After the initial Vivian Smith funding, the work was awarded funding by the Juvenile Diabetes Research Foundation (JDRF): $200,000 for a proof-of-concept device. Then, internal funding from a pilot program created by Dirk Sostman, MD, at Houston Methodist provided another $250,000 for two years and they were able to leverage that into two more JDRF awards. With this new R01, the project currently has a combined $7 million in funding that will facilitate more preclinical studies, including a grant to specifically look at NICHE in non-human primates. The newly awarded NIH R01 will allow the team to study several aspects of the NICHE platform in a diabetic small animal preclinical model. They will investigate the ability of mesenchymal stem cells to induce vascularization within the NICHE as well as modulate the NICHE immune microenvironment to be conducive to islet transplantation. This will be followed by the biodistribution analysis of immunosuppressants locally eluted in the NICHE and the assessment of immunomodulation and pharmacokinetics. Then they will evaluate efficacy of the NICHE in providing a suitable environment for successful islet engraftment to restore euglycemia in their model, assessed over the course of one year, in parallel to a longitudinal study of NICHE microenvironment remodeling. Perhaps most importantly, design of the NICHE prioritizes clinical considerations of efficacy, safety and user acceptability. Cell and drug refilling of the NICHE reservoirs is transcutaneous and so can be done without removing the device, which allows for ease of drug replenishment when needed, thus extending implant lifespan potentially for the lifetime of patients. Further, the thin and compact size of the NICHE, which is smaller than the encapsulation implants under clinical investigation, is favorable for user acceptability. Successful completion of the proposed work will provide a broadly applicable encapsulation system with localized immunosuppressant delivery for long-term protection of transplanted islets, while minimizing adverse effects associated with immunosuppressive drugs. This could translate to a clinical breakthrough for deployment of cell therapies beyond islets, including stem cell-derived β cells, to treat diabetes as well as other diseases.