幹細胞生物学の最前線とその再生医療への応用

Summary The iPS technology opened up the way to patient-specific cell therapy, but it provided a novel tool to study developmental processes, mechanisms of various human disease, drug efficacy, toxicology and so on. Here, I describe two projects that have been going on in my laboratory. First, we established an in vitro culture system whereby hESCs or hiPSCs can be differentiated into megakaryocytes and functional platelets. Furthermore, we found that these human iPSC-derived platelets can form thrombus together with mouse platelets in vivo. The results indicated that hESCs and hiPSCs can be potential sources for platelet production and that this system will contribute to understanding the mechanism of various genetic platelet disorders and to development of novel cell/gene therapy. Second, we established a protocol to generate a solid organ using hiPSCs in xenogenic environment. When wild type rat iPSCs were injected into mouse Pdx1-/- blastocysts, in newborn mice, defective cells were totally replaced and pancreas was formed almost entirely by injected rat iPSCderived cells. Chimeric mice of Pdx1-/- genotype survived to adulthood without any sign of diabetes. Generation of organs using rat iPSCs and blastocyst complementation in vivo provides a new strategy for understanding organogenesis and a novel approach for organ supply.