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

2015; Nature Portfolio; Volume: 17; Issue: 8 Linguagem: Inglês

10.1038/ncb3205

1476-4679

Christoph Patsch, Ludivine Challet-Meylan, Eva Thoma, Eduard Urich, Tobias Heckel, John O’Sullivan, Stephanie Grainger, Friedrich Kapp, Lin Sun, Klaus Christensen, Yulei Xia, Mary H.C. Florido, Wei He, Wei Pan, Michael Prummer, Curtis R. Warren, Roland Jakob‐Roetne, Ulrich Certa, Ravi Jagasia, Per‐Ola Freskgård, Isaac Adatto, Dorothée Kling, Paul L. Huang, Leonard I. Zon, Elliot L. Chaikof, Robert E. Gerszten, Martin Graf, Roberto Iacone, Chad A. Cowan,

Renal and related cancers

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. Cowan and colleagues report a method to generate mature endothelial or vascular smooth muscle cells from human pluripotent stem cells with high efficiency and purity.