Exploiting human iPS cell-derived cardiovascular cell populations toward cardiac regenerative therapy

Abstract

To achieve induced pluripotent stem cell (iPSC)-based cardiac regenerative therapy, it is indispensable to establish a method to efficiently induce cardiovascular cell populations from human iPSCs (hiPSCs). We have previously reported a novel serum-free high-density monolayer culture method to induce cardiomyocytes (CMs) from hiPSCs using a stage-specific sequential treatment with TGFβ superfamily molecules (Activin A and BMP4) and a canonical Wnt antagonist, Dkk1. We also succeeded in purifying the differentiated CMs by cell sorting, immunologically labelling the vascular cell adhesion molecule-1 (VCAM-1), a CM-specific cell surface marker which was determined by cell surface marker screening. To induce vascular cells along with CMs, we modified the CM induction method using vascular endothelial cell growth factor on mesoderm-staged cells, which led to simultaneous induction of CMs and vascular cells. We reassembled the cardiovascular cell populations to form a cell sheet which showed a potential for cardiac functional recovery in a rodent myocardial infarction model. These cell differentiation toward cardiovascular cell populations from hiPSCs and bioengineered transplantation methods, could potentially promote hiPSC-based cardiac regenerative therapy in the future.