Differentiation of human pluripotent stem cells into functional CD34+ progenitor cells by combined modulation of signaling pathways

Abstract

Efficient and directed differentiation of human pluripotent stem cells (hPSCs) into functional cell types is a major bottleneck for the realization of stem cell therapy. However, efficient differentiation methods in both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) should be further investigated. Here, I suggest that functional CD34+ vascular progenitor cells can be efficiently produced by combined modulation of two signaling pathways in hESCs and hiPSCs. The proportion of CD34+ cells (?? 20%) was synergistically enhanced by inhibition of MEK/ERK signaling and activation of BMP4. These hESC-derived CD34+ progenitor cells further developed to endothelial and smooth muscle cells with functionality. Moreover, hESC- and hiPSC-derived CD34+ progenitor cells could be contributed directly to neovasculogenesis in ischemic mouse hindlimbs, thereby resulting in improved blood perfusion and limb salvage. Our results show that combined modulation of signaling pathways may be an efficient means of differentiating hESCs and hiPSCs into functional CD34+ progenitor cells.