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 Murphy, Shahin Rafii, Hal Broxmeyer, Mervin Yoder

Research output: Contribution to journalArticle

106 Scopus citations

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 (US)
Pages (from-to)1151-1157
Number of pages7
JournalNature Biotechnology
Volume32
Issue number11
DOIs
StatePublished - 2014

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ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine(all)
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology

Cite this

Prasain, N., Lee, M. R., Vemula, S., Meador, J. L., Yoshimoto, M., Ferkowicz, M. J., Fett, A., Gupta, M., Rapp, B. M., Saadatzadeh, M. R., Ginsberg, M., Elemento, O., Lee, Y., Voytik-Harbin, S. L., Chung, H. M., Hong, K. S., Reid, E., O'Neill, C. L., Medina, R. J., ... Yoder, M. (2014). Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells. Nature Biotechnology, 32(11), 1151-1157. https://doi.org/10.1038/nbt.3048