Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 19, Issue 5, Pages 1315-1327Publisher
WILEY
DOI: 10.1111/ajt.15168
Keywords
antigen presentation/recognition; autoimmunity; basic (laboratory) research/science; bioengineering; diabetes: type 1; graft survival; islet transplantation; regenerative medicine
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Funding
- JDRF [2-SRA-2014-287-Q-R, 3-SRA-2015-38-Q-R]
- National Institutes of Health [U01 AI132817]
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Transplant of hydrogel-encapsulated allogeneic islets has been explored to reduce or eliminate the need for chronic systemic immunosuppression by creating a physical barrier that prevents direct antigen presentation. Although successful in rodents, translation of alginate microencapsulation to large animals and humans has been hindered by large capsule sizes (>= 500 mu m diameter) that result in suboptimal nutrient diffusion in the intraperitoneal space. We developed a microfluidic encapsulation system that generates synthetic poly(ethylene glycol)-based microgels with smaller diameters (310 +/- 14 mu m) that improve encapsulated islet insulin responsiveness over alginate capsules and allow transplant within vascularized tissue spaces, thereby -reducing islet mass requirements and graft volumes. By delivering poly(ethylene glycol)-encapsulated islets to an isolated, retrievable, and highly vascularized site via a vasculogenic delivery vehicle, we demonstrate that a single pancreatic donor syngeneic islet mass exhibits improved long-term function over conventional alginate capsules and close integration with transplant site vasculature. In vivo tracking of bioluminescent allogeneic encapsulated islets in an autoimmune type 1 diabetes murine model showed enhanced cell survival over unencapsulated islets in the absence of chronic systemic immunosuppression. This method demonstrates a translatable alternative to intraperitoneal encapsulated islet transplant.
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