Author + information
- Feng Wu1
Islets transplantation holds promise as a long term treatment to Type I diabetes. We have previously reported that bone marrow (BM) cells co-cultured with human islets generate a microenvironment suitable for repairing islets and promoting longevity. However, overcoming immunorejection is still a great challenge. We hypothesize that encapsulated islet/BM enhances human islet function while preventing immunorejection.
APA encapsulation was established by coating gel beads with additional layers of poly-L-ornithine and alginate to create a 4-layered immunoisolatory membrane. Fresh human islets were co-encapsulated with or without fresh human BM (1, 5 and 10 x 106) in APA microcapsules and the optimal ratio of BM to islets was studied based on insulin secretion using ELISA.
No labeled peripheral blood cells (PBCs) were observed inside the capsule with human islets, indicating the APA encapsulation isolated human islets from PBCs to create a unique microenvironment free from potential interaction with host immune responses. Human islets (2500 IEQ) co-encapsulated with 5 x 106 BM generated the most optimal results over a 5 week culture period. After 4 weeks of culture, encapsulated human islets with BM formed a 3D structure while groups without encapsulation formed a 2D structure. Encapsulated human islets with 5 x 106 BM released more insulin when stimulated than groups without encapsulation under otherwise the same conditions.
Our results show encapsulated human islets with 5 x 106 BM can create a microenvironment benefitting human islet function/longevity while preventing immunorejection. Further developing this approach will create optimized human islets to enhance islet transplantation.