The Survival and Function of Whole or Dissociated Islet Transplants Are Improved by Immunomodulatory Microporous Annealed Particle (MAP) Gel

The aim was to investigate if MAP gel can support the function of whole islets or dissociated islet cells, and improve transplantation under kidney capsule or within the epididymal fat pad. A) Whole or dissociated BL/6 islets were transplanted into syngeneic diabetic recipients in the presence or absence of MAP gel. 100 islets were transplanted under the kidney capsule (n=6/group). Mice receiving transplant within the fat pad were divided into 6 groups (n=2/group): 300 whole islets; 400 dissociated islets; MAP gel alone; and 200, 300 or 400 dissociated islets with MAP gel. Blood glucose (BG) was measured daily. B) MAP gel or NP gel was transplanted within the fat pad of NOD mice (n=4/group) to analyze the immune response. Graft-containing fat pad was excised 6 weeks post-transplantation and analyzed for cytokines by flow cytometry. Our results indicated that transplantation of dissociated islets and MAP gel under the kidney capsule permanently restored normoglycemia within 18 days. In contrast, uncoated dissociated islet cells failed to reverse diabetes. Treatment efficacy continued 40 days post-transplantation, the entire period of observation. At Day 30, average BG was 163±38mg/dL. Diabetic mice transplanted with dissociated islet cells without MAP gel remained hyperglycemic. Transplantation of 400 dissociated islet cells with MAP gel within the fat pad also achieved normal BG levels that continued 44 days post-transplantation, the period of observation. In contrast, transplantation of MAP gel, or 300 whole islets, or dissociated islets alone into the fat pad, failed to reverse diabetes. An upregulation of IL-10 and downregulation of IL-6 was observed only in the graft microenvironment of the MAP gel group, validating the immunomodulating capacity of MAP gel. To conclude, MAP gel can promote transplantation outcomes under the kidney capsule or within the fat pad by improving the survival and function of both, whole and dissociated islets. Disclosure M.Ma: None. C.A.Roosa: None. D.R.Griffin: Board Member; Tempo Therapeutics. K.L.Brayman: None. P.Chhabra: None. Funding LaunchPad for Diabetes Innovation Fund (GF004946); LaunchPad for Diabetes Ignite Program (169098)