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

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

Fingerprint

Pluripotent Stem Cells
Stem cells
Fetal Blood
Blood
Neuropilin-1
Endothelial cells
Blood vessels
Repair
Chemical activation
Induced Pluripotent Stem Cells
Teratoma
Embryonic Stem Cells
Vascular Diseases
Blood Vessels
Retina
Extremities
Endothelial Cells
Maintenance
Phenotype

ASJC Scopus subject areas

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

Cite this

Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells. / Prasain, Nutan; Lee, Man Ryul; Vemula, Sasidhar; Meador, Jonathan Luke; Yoshimoto, Momoko; Ferkowicz, Michael J.; Fett, Alexa; Gupta, Manav; Rapp, Brian M.; Saadatzadeh, Mohammad Reza; Ginsberg, Michael; Elemento, Olivier; Lee, Younghee; Voytik-Harbin, Sherry L.; Chung, Hyung Min; Hong, Ki Sung; Reid, Emma; O'Neill, Christina L.; Medina, Reinhold J.; Stitt, Alan W.; Murphy, Michael; Rafii, Shahin; Broxmeyer, Hal; Yoder, Mervin.

In: Nature Biotechnology, Vol. 32, No. 11, 2014, p. 1151-1157.

Research output: Contribution to journalArticle

Prasain, N, Lee, MR, Vemula, S, Meador, JL, Yoshimoto, M, Ferkowicz, MJ, Fett, A, Gupta, M, Rapp, BM, Saadatzadeh, MR, Ginsberg, M, Elemento, O, Lee, Y, Voytik-Harbin, SL, Chung, HM, Hong, KS, Reid, E, O'Neill, CL, Medina, RJ, Stitt, AW, Murphy, M, Rafii, S, Broxmeyer, H & Yoder, M 2014, 'Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells', Nature Biotechnology, vol. 32, no. 11, pp. 1151-1157. https://doi.org/10.1038/nbt.3048
Prasain, Nutan ; Lee, Man Ryul ; Vemula, Sasidhar ; Meador, Jonathan Luke ; Yoshimoto, Momoko ; Ferkowicz, Michael J. ; Fett, Alexa ; Gupta, Manav ; Rapp, Brian M. ; Saadatzadeh, Mohammad Reza ; Ginsberg, Michael ; Elemento, Olivier ; Lee, Younghee ; Voytik-Harbin, Sherry L. ; Chung, Hyung Min ; Hong, Ki Sung ; Reid, Emma ; O'Neill, Christina L. ; Medina, Reinhold J. ; Stitt, Alan W. ; Murphy, Michael ; Rafii, Shahin ; Broxmeyer, Hal ; Yoder, Mervin. / Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells. In: Nature Biotechnology. 2014 ; Vol. 32, No. 11. pp. 1151-1157.
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AU - Hong, Ki Sung

AU - Reid, Emma

AU - O'Neill, Christina L.

AU - Medina, Reinhold J.

AU - Stitt, Alan W.

AU - Murphy, Michael

AU - Rafii, Shahin

AU - Broxmeyer, Hal

AU - Yoder, Mervin

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