Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells

作者：Patsch Christoph^*; Challet Meylan Ludivine; Thoma Eva C; Urich Eduard; Heckel Tobias; O'Sullivan John F; Grainger Stephanie J; Kapp Friedrich G; Sun Lin; Christensen Klaus; Xia Yulei; Florido Mary H C; He Wei; Pan Wei; Prummer Michael; Warren Curtis R; Jakob Roetne Roland; Certa Ulrich; Jagasia Ravi; Freskgard Per Ola; Adatto Isaac; Kling Dorothee; Huang Paul; Zon Leonard I; Chaikof Elliot L; Gerszten Robert E; Graf Martin; Iacone Roberto; Cowan Chad A

来源：Nature Cell Biology, 2015, 17(8): 994-U294.

DOI：10.1038/ncb3205

The use of human pluripotent stem cells for in vitro disease modelling and clinical applications requires protocols that convert these cells into relevant adult cell types. Here, we report the rapid and efficient differentiation of human pluripotent stem cells into vascular endothelial and smooth muscle cells. We found that GSK3 inhibition and BMP4 treatment rapidly committed pluripotent cells to a mesodermal fate and subsequent exposure to VEGF-A or PDGF-BB resulted in the differentiation of either endothelial or vascular smooth muscle cells, respectively. Both protocols produced mature cells with efficiencies exceeding 80% within six days. On purification to 99% via surface markers, endothelial cells maintained their identity, as assessed by marker gene expression, and showed relevant in vitro and in vivo functionality. Global transcriptional and metabolomic analyses confirmed that the cells closely resembled their in vivo counterparts. Our results suggest that these cells could be used to faithfully model human disease.

• 出版日期2015-8