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Nat Biotechnol. 2014 Nov;32(11):1151-1157. doi: 10.1038/nbt.3048. Epub 2014 Oct 12.

Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells.

Author information

1
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
2
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
3
Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
4
Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA.
5
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA.
6
Department of Medicine, the University of Chicago, Chicago, Illinois, USA.
7
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
8
Kon Kuk University School of Medicine, Seoul, South Korea.
9
Stem Cell Research Laboratory, CHA University, Seoul, South Korea.
10
Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.
#
Contributed equally

Abstract

The ability to differentiate human pluripotent stem cells into endothelial cells with properties of cord-blood endothelial colony-forming cells (CB-ECFCs) may enable the derivation of clinically relevant numbers of highly proliferative blood vessel-forming cells to restore endothelial function in patients with vascular disease. We describe a protocol to convert human induced pluripotent stem cells (hiPSCs) or embryonic stem cells (hESCs) into cells similar to CB-ECFCs at an efficiency of >10(8) ECFCs produced from each starting pluripotent stem cell. The CB-ECFC-like cells display a stable endothelial phenotype with high clonal proliferative potential and the capacity to form human vessels in mice and to repair the ischemic mouse retina and limb, and they lack teratoma formation potential. We identify Neuropilin-1 (NRP-1)-mediated activation of KDR signaling through VEGF165 as a critical mechanism for the emergence and maintenance of CB-ECFC-like cells.

PMID:
25306246
PMCID:
PMC4318247
DOI:
10.1038/nbt.3048
[Indexed for MEDLINE]
Free PMC Article

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