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

作者：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; Gin**erg 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 P; Rafii Shahin; Broxmeyer Hal E; Yoder Mervin C^*

来源：Nature Biotechnology, 2014, 32(11): 1151-1157.

DOI：10.1038/nbt.3048

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 %26gt;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.

• 出版日期2014-11