48: Islets Loaded in Hydrogel Derived from Human Amniotic Membrane Reverse Diabetes in Mice

Abstract

Background Development of macroencapsulation, neovascularized devices and biopolymer scaffolds that could be easily loaded with islets and implanted, with the aim of constructing a bioartificial pancreas may help to reduce the risks and improve the success rate of islet transplantation. Human amniotic membrane (HAM) is inexpensive and attractive as a biomaterial due to its structural similarities to islet extracellular matrix (ECM), and its immunomodulatory, anti-inflammatory and antifibrotic properties. The aim of our study was to develop hydrogel derived from HAM and assess whether it could support islet function in vitro and in vivo. Methods/ Materials The hydrogels were generated from HAM and accessed for porosity and ECM content. The protein content in HAM derived hydrogels and native HAM lysates were measured. To assess hydrogel impact on islet viability and function isolated rat islets were incorporated into the hydrogels and cultured for one week. The cell viability was evaluated by FDA/PI staining. To demonstrate islet function the glucose stimulated insulin secretion (GSIS) tests were performed using standard ELISA. Next, we assessed whether incorporation of islets into hydrogel could enhance engraftment and lead to better glycemic control in diabetic SCID mice. For this purpose 350 rat islets (IEQ) loaded into the hydrogels or islets alone (control) were transplanted into the epididymal fat of diabetic SCID mice. Blood glucose levels were monitored daily and intraperitoneal glucose tolerance tests (IPGTTs) were carried out. Grafts and serum were harvested at 1, 2, 6 and 12 weeks after transplantation to assess outcome. Results The ECM concentration in the hydrogel affected the pore size. Insulin and glucagon expression and viability of islets incorporated into hydrogel was significantly higher than that of islets in free-floating culture. In addition, significant enhancement of GSIS was observed from islets embedded in hydrogel as compared to controls. In vivo experiments showed that, transplantation of 350 IEQ embedded in hydrogel lead to enhanced engraftment, vascularization, viability and better glycaemic control compared to control mice transplanted with islets alone. Conclusions Incorporation of pancreatic islet into amnion-derived hydrogels enhances islet engraftment and is a valuable approach to improve islet transplantation outcomes. This work was supported by a grant from the Swiss National Science Foundation (Grant #310030_173138, to TB, EB, DB) and a grant from the European Foundation for Study of Diabetes (to EB and DB).