Abstract
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 μm 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 μm) 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.
Original language | English (US) |
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Pages (from-to) | 1315-1327 |
Number of pages | 13 |
Journal | American Journal of Transplantation |
Volume | 19 |
Issue number | 5 |
DOIs | |
State | Published - May 2019 |
Externally published | Yes |
Keywords
- antigen presentation/recognition
- autoimmunity
- basic (laboratory) research/science
- bioengineering
- diabetes: type 1
- graft survival
- islet transplantation
- regenerative medicine
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)