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 Stitt; Michael P Murphy; Shahin Rafii; Hal E Broxmeyer; Mervin C Yoder

doi:10.1038/nbt.3048

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 journal › Article › peer-review

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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 language	English
Pages (from-to)	1151-1157
Number of pages	7
Journal	Nature Biotechnology
Volume	32
Issue number	11
Early online date	12 Oct 2014
DOIs	https://doi.org/10.1038/nbt.3048
Publication status	Published - Nov 2014

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Alan Stitt
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- School of Medicine, Dentistry and Biomedical Sciences - Dean of Innovation and Impact
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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. C. (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

@article{b3480317077a4f4cb5e60dda0ddb6916,

title = "Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells",

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.",

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

year = "2014",

month = nov,

doi = "10.1038/nbt.3048",

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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, MP, Rafii, S, Broxmeyer, HE & Yoder, MC 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

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T1 - Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells

AU - Prasain, Nutan

AU - Lee, Man Ryul

AU - Vemula, Sasidhar

AU - Meador, Jonathan Luke

AU - Yoshimoto, Momoko

AU - Ferkowicz, Michael J

AU - Fett, Alexa

AU - Gupta, Manav

AU - Rapp, Brian M

AU - Saadatzadeh, Mohammad Reza

AU - Ginsberg, Michael

AU - Elemento, Olivier

AU - Lee, Younghee

AU - Voytik-Harbin, Sherry L

AU - Chung, Hyung Min

AU - Hong, Ki Sung

AU - Reid, Emma

AU - O'Neill, Christina L

AU - Medina, Reinhold J

AU - Stitt, Alan W

AU - Murphy, Michael P

AU - Rafii, Shahin

AU - Broxmeyer, Hal E

AU - Yoder, Mervin C

PY - 2014/11

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AB - 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.

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EP - 1157

JO - Nature Biotechnology

JF - Nature Biotechnology

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ER -

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

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