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

Nutan Prasain, Man Ryul Lee, Sasidhar Vemula, Jonathan Luke Meador, Momoko Yoshimoto, Michael J Ferkowicz, Alexa Fett, Manav Gupta, Brian M Rapp, Mohammad Reza Saadatzadeh, Michael Ginsberg, Olivier Elemento, Younghee Lee, Sherry L Voytik-Harbin, Hyung Min Chung, Ki Sung Hong, Emma Reid, Christina L O'Neill, Reinhold J Medina, Alan W StittMichael P Murphy, Shahin Rafii, Hal E Broxmeyer, Mervin C Yoder

Research output: Contribution to journalArticle

118 Citations (Scopus)

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 >108 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.

Original languageEnglish
Pages (from-to)1151-1157
Number of pages7
JournalNature Biotechnology
Volume32
Issue number11
Early online date12 Oct 2014
DOIs
Publication statusPublished - Nov 2014

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