Monkeying around with cardiac progenitors: hope for the future

Abstract

Multipotent cardiovascular progenitor cells derived from ES cells or induced pluripotent stem (iPS) cells are an intriguing source for stem cell-based therapies for congenital and acquired heart diseases. From a clinical perspective, the ideal cardiac progenitor cells are those that can proliferate, survive, and differentiate into multiple mature cardiac cell types when transplanted into normal or diseased heart. In this issue of JCI, Blin et al. report the isolation and characterization of a group of early mesodermal cardiovascular progenitor cells, induced by BMP2 and marked by the cell surface protein, stage-specific embryonic antigen 1 (SSEA-1). BMP2-induced SSEA-1+ cells were purified from ES and iPS cells and could be directed to differentiate into cardiomyocytes, endothelial cells, and smooth muscle cells by treatment with defined cytokines and signaling molecules. Most importantly, purified SSEA+ progenitor cells from Rhesus monkey ES cells engrafted into nonhuman primate hearts, in which they differentiated into cardiac cells without forming teratomas. These findings move the field another step closer to clinical use of ES or iPS cell-derived cardiovascular progenitors in cardiac repair.

Figure 1. Schematic of primate BMP2-induced SSEA-1⁺ cells.

Epiblast cells in the embryo express the surface marker SSEA-1 as they differentiate and transiently express Oct4 and Mesp1 during the commitment to CPCs. Blin et al. show that using BMP2 to mimic the environment of epiblast cells, primate ES and iPS cells can be induced to differentiate into SSEA-1⁺ CPCs. Isolated BMP2-induced SSEA-1⁺ cells were multipotent CPCs that could be differentiated into endothelial cells, smooth muscle cells, and cardiomyocytes under different growth conditions. The SSEA-1⁺ cells were also multipotent in vivo upon transplantation into primate hearts.