Delivery of Dissociated Islets Cells within Microporous Annealed Particle Scaffold to Treat Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is caused by the autoimmune loss of insulin-producing beta cells in the pancreas. The only clinical approach to patient management of blood glucose that doesn't require exogenous insulin is pancreas or islet transplantation. Unfortunately, donor islets are scarce and there is substantial islet loss immediately after transplantation due, in part, to the local inflammatory response. The delivery of stem cell-derived beta cells (e.g., from induced pluripotent stem cells) and dissociated islet cells hold promise as a treatment for T1D; however, these cells typically require re-aggregation in vitro prior to implantation. Microporous scaffolds have shown high potential to serve as a vehicle for organization, survival, and function of insulin-producing cells. In this study, the use of microporous annealed particle (MAP) scaffold for delivery of enzymatically dissociated islet cells, a model beta cell source, within the scaffold's interconnected pores is investigated. It is found that MAP-based cell delivery enables survival and function of dissociated islets cells both in vitro and in an in vivo mouse model of T1D.