Future treatment of heart failure using human iPSC-derived cardiomyocytes

Heart transplantation can drastically improve survival in patients with a failing heart; however, the shortage of donor hearts remains a serious problem with this treatment strategy and the successful clinical application of regenerative medicine is eagerly awaited. To this end, we developed a novel method to generate human induced pluripotent stem cells (iPSCs) from circulating human T lymphocytes using Sendai virus containing Yamanaka factors. To establish an efficient cardiac differentiation protocol, we then screened factors expressed in the future heart site of early mouse embryos and identified several growth factors and cytokines that can induce cardiomyocyte differentiation and proliferation. Subsequent transcriptome and metabolome analysis on undifferentiated stem cells and cardiomyocytes to devise a specific metabolic environment for cardiomyocyte selection revealed completely different mechanisms of glucose and lactate metabolism. Based on these findings, we succeeded in metabolically selecting cardiomyocytes using glucose-free and lactate-supplemented medium, with up to 99 % purity and no teratoma formation. Using our aggregation technique, we also showed that >90 % of the transplanted cardiomyocytes survived in the heart and showed physiological growth after transplantation. We expect that combining these techniques will achieve future heart regeneration.