Developing large-scale bioreactor protocols to expand pancreatic endocrine tissue to treat type 1 diabetes

Abstract

Type 1 diabetes is a disease of the pancreas in which the beta islet (endocrine) cells, which are responsible for insulin production, are destroyed by the immune system. The expansion in bioreactors and subsequent transplantation of endocrine cells could revolutionize the treatment for Type 1 diabetes using the "world-famous" Edmonton Protocol. Consequently, the aim of this study was to develop a scaleable process to expand mammalian pancreatic endocrine tissue in suspension bioreactors. Issues regarding cell culture medium conditions and cell handling protocols were investigated. Experiments in suspension bioreactors for 9 days showed a greater than 7-fold increase in the number of insulin-positive cells. Furthermore, aggregates were islet-like, as all of the endocrine cell types were present. Most importantly, cells exhibited glucose-responsive behavior and thus functionality.. These results represent a major milestone on the path to effective expansion and clinical use of bioreactor-produced islet-like structures in the treatment of Type 1 diabetes.