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

Nature cell biology, 2015-08, Vol.17 (8), p.994-1003 [Peer Reviewed Journal]

COPYRIGHT 2015 Nature Publishing Group ;COPYRIGHT 2015 Nature Publishing Group ;Copyright Nature Publishing Group Aug 2015 ;ISSN: 1465-7392 ;EISSN: 1476-4679 ;DOI: 10.1038/ncb3205 ;PMID: 26214132

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Title:
Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells
Author: 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 ; Freskgård, Per-Ola ; Adatto, Isaac ; Kling, Dorothee ; Huang, Paul ; Zon, Leonard I ; Chaikof, Elliot L ; Gerszten, Robert E ; Graf, Martin ; Iacone, Roberto ; Cowan, Chad A
Subjects: Animals ; Biomarkers - metabolism ; Bone Morphogenetic Protein 4 - pharmacology ; Cell differentiation ; Cell Differentiation - drug effects ; Cell Line ; Cell Lineage - drug effects ; Cell research ; Coculture Techniques ; Dose-Response Relationship, Drug ; Endothelial Cells - drug effects ; Endothelial Cells - enzymology ; Endothelial Cells - physiology ; Endothelial Cells - transplantation ; Endothelium ; Gene Expression Profiling - methods ; Gene Expression Regulation, Developmental ; Glycogen Synthase Kinase 3 - antagonists & inhibitors ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 beta ; Growth ; Human Umbilical Vein Endothelial Cells - physiology ; Humans ; Induced Pluripotent Stem Cells - drug effects ; Induced Pluripotent Stem Cells - enzymology ; Induced Pluripotent Stem Cells - physiology ; Induced Pluripotent Stem Cells - transplantation ; Metabolomics - methods ; Mice, Inbred NOD ; Mice, SCID ; Muscle cells ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - enzymology ; Muscle, Smooth, Vascular - physiology ; Muscle, Smooth, Vascular - transplantation ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - enzymology ; Myocytes, Smooth Muscle - physiology ; Myocytes, Smooth Muscle - transplantation ; Neovascularization, Physiologic ; Phenotype ; Protein Kinase Inhibitors - pharmacology ; Proto-Oncogene Proteins c-sis - pharmacology ; Stem cells ; Time Factors ; Transcription, Genetic ; Transfection ; Vascular Endothelial Growth Factor A - pharmacology ; Wnt Signaling Pathway - drug effects
Is Part Of: Nature cell biology, 2015-08, Vol.17 (8), p.994-1003
Description: 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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 1465-7392
EISSN: 1476-4679
DOI: 10.1038/ncb3205
PMID: 26214132
Source: AUTh Library subscriptions: ProQuest Central
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Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells

COPYRIGHT 2015 Nature Publishing Group ;COPYRIGHT 2015 Nature Publishing Group ;Copyright Nature Publishing Group Aug 2015 ;ISSN: 1465-7392 ;EISSN: 1476-4679 ;DOI: 10.1038/ncb3205 ;PMID: 26214132

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