Long-Term Survival of Nonhuman Primate Islets Implanted in an Omental Pouch on a Biodegradable Scaffold

Abstract

The aim of this study was to test whether an omental pouch can be used as an alternative site for islet implantation in diabetic monkeys. Here we report the successful engraftment of islets in diabetic cynomolgus monkeys when loaded on a synthetic biodegradable scaffold and placed in an omental pouch. One autologous and 5 allogeneic diabetic monkey transplants under the cover of steroid-free immune suppression were undertaken. Fasting blood glucose (FBG) and c-peptide (CP), exogenous insulin requirements (EIR), intravenous glucose tolerance test (IVGTT), A1C and histopathology were used to assess islet engraftment and survival. All animals achieved CP levels > 1.0 ng/ml following transplant, a 66 – 92% post-transplant decrease in EIR and reduced A1C. Following graft removal, CP became negative and histopathological analysis of the explanted grafts demonstrated well granulated and well vascularized, insulin positive islets, surrounded by T cell subsets and macrophages. Compared to intrahepatic allogeneic islet transplants (n=20), there was a delayed engraftment for omental pouch recipients but similar levels of CP production were ultimately achieved, with a broad range of IEQ/kg transplanted in both sites. Our results suggest this extrahepatic transplantation site has potential as an alternative site for clinical islet cell transplantation.

Human islet cell implants in a nude rat model of diabetes survive better in omentum than in liver with a positive influence of beta cell number and purity

“…The omentum has been previously used for transplantation of islets from rats, dogs and cynomologus monkeys in syngeneic and allogeneic combinations [19][20][21][22][23][24]. Cultured rat islet cell grafts with higher endocrine purity were examined in parallel.…”

Encapsulation technologies in beta cell replacement therapies for Type 1 diabetes

“…However, several challenges still remain unaddressed. Advances in bioencapsulation technologies and biomaterial manufacturing, and improvements in islet and stem cell yields and insulin release parameters, along with the development of standard operating procedures (SOP), quality control measures and stringent guidelines and are vital to achieve seamless translation of these promising therapies to clinical practice with the ultimate goal of reduced patient morbidity, mortality, better quality of life and long--lasting insulin independence [192].…”

Enhancing Clinical Islet Transplantation through Tissue Engineeering Strategies

“…[40][41][42][43] This site has clinical relevance and is feasible in larger animal models, further justifying the need for additional investigations as to its potential. 25,44 …”