期刊
STEM CELL REPORTS
卷 3, 期 5, 页码 804-816出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2014.09.005
关键词
-
资金
- NIH [R01 EB007534, R21 NS085351]
- Takeda Pharmaceuticals
- NIH Chemistry Biology Interface Training [NIGMS T32 GM008505]
Human pluripotent stem cell (hPSC)-derived endothelial cells and their progenitors may provide the means for vascularization of tissue-engineered constructs and can serve as models to study vascular development and disease. Here, we report a method to efficiently produce endothelial cells from hPSCs via GSK3 inhibition and culture in defined media to direct hPSC differentiation to CD34(+)CD31(+) endothelial progenitors. Exogenous vascular endothelial growth factor (VEGF) treatment was dispensable, and endothelial progenitor differentiation was beta-catenin dependent. Furthermore, by clonal analysis, we showed that CD34(+) CD31(+) CD117(+) TIE-2(+) endothelial progenitors were multipotent, capable of differentiating into calponin-expressing smooth muscle cells and CD31(+) CD144(+) vWF(+) I-CAM1(+) endothelial cells. These endothelial cells were capable of 20 population doublings, formed tube-like structures, imported acetylated low-density lipoprotein, and maintained a dynamic barrier function. This study provides a rapid and efficient method for production of hPSC-derived endothelial progenitors and endothelial cells and identifies WNT/beta-catenin signaling as a primary regulator for generating vascular cells from hPSCs.
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