Pancreatic islet transplantation is a promising cell therapy to treat type 1 (juvenile) diabetes, but this strategy is severely limited by insufficient donor islet supply and islet loss due to inflammatory reactions, lack of vascularization, and immune rejection. The García lab has engineered synthetic hydrogels for controlled delivery of the vasculogenic protein VEGF that promote islet survival, engraftment and function. In a separate project, the García group engineered hydrogel particles that present the potent immunomodulatory protein FasL and showed that allogeneic islets co-transplanted with these materials were engrafted and cured diabetes in mice for over 200 days without systemic immunosuppression regimens. This is a major advance in the field, and the group is currently evaluating this strategy in diabetic non-human primates.
- Weaver JD, Headen DM, Aquart J, Johnson CT, Shea LD, Shirwan H, García AJ. Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. Science Adv 2017; 3(6):e1700184. PMC5457148.
- Weaver JD, Headen DM, Hunckler MD, Coronel MM, Stabler CL, García AJ. Design of a vascularized synthetic poly(ethylene glycol) macroencapsulation device for islet transplantation. Biomaterials 2018; 172: 54-65. PMC5967258
- Headen DM, Woodward KB, Coronel MM, Shrestha P, Weaver JD, Zhao H, Tan M, Hunckler MD, Bowen WS, Johnson CT, Shea L, Yolcu ES, García AJ, Shirwan H. Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance. Nat Mater 2018; 17: 732-739. PMC6060019.
- Weaver JD, Headen DM, Coronel MM, Hunckler MD, Shirwan H, García AJ. Synthetic poly(ethylene glycol)-based microfluidic islet encapsulation reduces graft volume for delivery to highly vascularized and retrievable transplant site. Am J Transplant 2018; Epub Oct 31. doi: 10.1111/ajt.15168. PMID: 30378751.