Mass production of functional beta islet-like clusters

Abstract Progress in the development of clinical cell transplantation therapy for Type Diabetes T D has been hindered due to the lack of patient specific inexhaustible human pancreatic islets that are immuno evasive Recent advances in stem cell differentiation have demonstrated the utility of human induced pluripotent stem cells hiPSCs as a valid cell source to produce patient specific renewable human pancreatic islets that are competent for glucose responsive insulin secretion However current technologies do not support scalable expansion and differentiation of hiPSCs for the production of high quality human pancreatic islets in large quantities to meet clinical demands The overall goal of this SBIR Phase I project is to develop enabling technologies for the mass production of hiPSC derived functional pancreatic islet like cell clusters ILCs for T D cell therapy through quick and serial expansion during the pancreatic differentiation process Using a thin wire array base cell aggregate cutter hiPSC derived cell aggregates at certain stage to be determined in the project will be reduced to uniform sized smaller aggregates which will continue to grow in culture After serial expansions the cell aggregates will proceed along their pancreatic differentiation pathway to ILCs Once the scalable expansion platform is developed we will characterize the biochemical profile and in vitro functionalities of the resultant ILCs Our overall hypothesis is that stage specific rapid and serial expansion of hiPSC derived cell aggregates during their stepwise pancreatic differentiation will not adversely affect their downstream pancreatic differentiation into pancreatic ILCs and the functionalities of the resultant hiPSC EB ILCs The work is expected to develop enabling technologies to overcome human pancreatic cell shortages representing key advances toward clinically applicable T D cell therapy that possesses immense commercial potential Project Narrative By developing an enabling technology that allows serial and rapid expansion of hiPSC derived cell aggregates during their pancreatic differentiation to generate functional human pancreatic islet like cell clusters ILCs this research holds great promise in mass production of physiologically competent patient specific inexhaustible glucose responsive insulin producing cells for T D cell therapy