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Nat Cell Biol. 2015 Aug;17(8):994-1003. doi: 10.1038/ncb3205. Epub 2015 Jul 27.

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

Author information

1
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
2
Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Massachusetts 02138, USA.
3
Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
4
1] Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 9F Boston, Massachusetts 02115, USA [2] The Wyss Institute of Biologically Inspired Engineering of Harvard University, Boston, Massachusetts 02115, USA.
5
Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
6
1] Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Massachusetts 02138, USA [2] Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
7
1] Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Massachusetts 02138, USA [2] Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA [3] Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

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.

PMID:
26214132
PMCID:
PMC4566857
DOI:
10.1038/ncb3205
[Indexed for MEDLINE]
Free PMC Article

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