Engineering an Endocrine Micro-Pancreas

Islet Transplantation has become a feasible cell therapy procedure that aims to achieve normoglycemia in severe diabetic patients. This procedure suffers from high percentage of islet lost, in part, due to lack of a proper microenvironment that is bound to be required for islet viability and function. We have recently described the preparation of engineered micro-pancreata (EMPs) that are made up of decellularaized organ-derived scaffolds of microscopic dimensions seeded with human intact or enzymatically dissociated islets and shown that EMPs secrete quantities of insulin per cell similar to freshly isolated human islets for more than three months in vitro in a glucose-regulated manner. We have now performed initial in vivo experiments, and show that EMPs can rescue hyperglycemic mice for long periods of three months in vivo with high levels of circulating human c-peptide. Removal of the EMPs one month after implantation results in a very rapid increase of glucose levels and death. Immunofluorescence staining show healthy vascularized islets within the micro-scaffolds that stain positive for glucagon, insulin and endothelial cell markers even 90 days after implantation.