Multipotent Vasculogenic Pericytes from Human Pluripotent Stem Cells Promote Recovery of Murine Ischemic Limb
Background—Pericytes represent a unique subtype of microvessel-residing perivascular cells with diverse angiogenic functions and multilineage developmental features of mesenchymal stem cells. Although various protocols for derivation of endothelial and/or smooth muscle cells from human pluripotent stem cells (hPSC, either embryonic or induced) have been described, the emergence of pericytes in the course of hPSC maturation was not elucidated yet.
Methods and Results—We found that during hPSC development, spontaneously differentiating embryoid bodies give rise to CD105+CD90+CD73+CD31- multipotent clonogenic mesodermal precursors, which can be isolated and efficiently expanded. Isolated and propagated cells expressed characteristic pericytic markers, including CD146, NG2 and PDGFR-β but not the SMC marker, α-smooth muscle actin. Co-implantation of hPSC-derived endothelial cells with pericytes resulted in functional and rapid anastomosis to the murine vasculature. Administration of pericytes into immuneodeficient mice with limb ischemia promoted significant vascular and muscle regeneration. At day 21 after transplantation recruited hPSC-pericytes were found incorporated into recovered muscle and vasculature.
Conclusions—Derivation of vasculogenic and multipotent pericytes from hPSC can be used for the development of vasculogenic models using multiple vasculogenic cell types for basic research and drug screening and can contribute to angiogenic regenerative medicine.
- Received June 8, 2011.
- Accepted October 11, 2011.
- Copyright © 2011, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited