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Experimental Islet Biology

Saturday October 23, 2021 - 12:00 to 13:30

Room: Virtual Room 2

402.7 Homemade hydrogel from human amniotic membrane improves islet transplantation outcomes in diabetic immunodeficient mice

Kevin Bellofatto, Switzerland

Post-doctoral assistant
Dpt of Surgery
Université de Genève

Abstract

Homemade hydrogel from human amniotic membrane improves islet transplantation outcomes in diabetic immunodeficient mice

Kevin Bellofatto1, Fanny Lebreton1, Charles-Henri Wassmer2, Masoud Hasany1,2, Reine Hanna1, Rahul Khatri1,2, Laura do Mar Fonseca1,2, Lisa Perez2, David Cottet-Dumoulin1, Géraldine Parnaud2, Domenico Bosco1, Thierry Berney2, Ekaterine Berishvili1,3.

1Surgery, Université de Genève, Geneva, Switzerland; 2Surgery, Hopitaux Universitaires de Genève, Geneva, Switzerland; 3Institute of Medical Research, Ilia State University, Tbilisi, Georgia

Background: Neovascularized devices and biopolymer scaffolds are getting a great attention for their potential to improve islet transplantations. Among many biomaterials sources, human amniotic membrane (HAM) is considered as a natural source to produce ECM-based hydrogels with immunomodulatory, anti-inflammatory and antifibrotic properties. Here we develop an ECM-based hydrogel (Amniogel) derived from HAM and evaluate its potential to support islet function in vitro and in vivo.

Methods: The Amniogels were generated from HAM and assessed for porosity, for ECM content and fibre integrity. To assess Amniogel impact on islet viability and function, isolated rat islets were incorporated into the Amniogel and cultured for one week. The cell viability was evaluated and islet function was assessed by a glucose stimulated insulin secretion (GSIS) test. We assessed whether incorporation of islets into the Amniogel could enhance engraftment and lead to better glycaemic control in diabetic Nod-Rag mice. For this purpose, 250 rat islets (IEQ) loaded into the Amniogel or islets alone (control) were transplanted into the epididymal fat of diabetic NSG mice. Blood glucose levels were monitored daily and intraperitoneal glucose tolerance tests were carried out. Grafts and serum were harvested at 1, 2, 6 and 12 weeks to assess outcome.

Results: The ECM concentration in the Amniogel affected the pore size. Insulin expression and viability of islets incorporated into Amniogel was significantly higher than inn the control group. In addition, significant enhancement of GSIS was observed from islets embedded in Amniogel. In vivo experiments showed that transplantation of 250 IEQ embedded in Amniogel lead to enhanced engraftment, vascularization, viability and better glycaemic control compared to control mice.

Conclusions: Incorporation of pancreatic islet into amnion-derived Amniogel enhances islet engraftment and is a valuable approach to improve islet transplantation outcomes.