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

被引:170
作者
Prasain, Nutan [1 ]
Lee, Man Ryul [2 ]
Vemula, Sasidhar [1 ]
Meador, Jonathan Luke [1 ]
Yoshimoto, Momoko [1 ]
Ferkowicz, Michael J. [1 ]
Fett, Alexa [1 ]
Gupta, Manav [1 ]
Rapp, Brian M. [3 ]
Saadatzadeh, Mohammad Reza [3 ]
Ginsberg, Michael [4 ]
Elemento, Olivier [5 ]
Lee, Younghee [6 ]
Voytik-Harbin, Sherry L. [7 ]
Chung, Hyung Min [8 ]
Hong, Ki Sung [9 ]
Reid, Emma
O'Neill, Christina L. [10 ]
Medina, Reinhold J. [10 ]
Stitt, Alan W. [10 ]
Murphy, Michael P. [3 ]
Rafii, Shahin [4 ]
Broxmeyer, Hal E. [2 ]
Yoder, Mervin C. [1 ]
机构
[1] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA
[2] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
[3] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA
[4] Weill Cornell Med Coll, Howard Hughes Med Inst, New York, NY USA
[5] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY USA
[6] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[7] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA
[8] Konkuk Univ, Sch Med, Seoul, South Korea
[9] CHA Univ, Stem Cell Res Lab, Seoul, South Korea
[10] Queens Univ Belfast, Ctr Expt Med, Belfast, Antrim, North Ireland
基金
新加坡国家研究基金会;
关键词
PROGENITOR CELLS; NEUROPILIN-1; TRANSPLANTATION; COMMITMENT; HIERARCHY; EXPANSION; OUTGROWTH; VEGF;
D O I
10.1038/nbt.3048
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 VEGF(165) as a critical mechanism for the emergence and maintenance of CB-ECFC-like cells.
引用
收藏
页码:1151 / 1157
页数:7
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