Progress in the development of clinical cell transplantation therapy for Type 1 Diabetes (T1D) 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 T1D 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 T1D cell therapy that possesses immense commercial potential.
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 T1D cell therapy.
