Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells
| Autor: | Wei He, Curtis R. Warren, Wei Pan, Michael Prummer, Leonard I. Zon, Friedrich G. Kapp, Ravi Jagasia, Robert E. Gerszten, Martin Graf, Ulrich Certa, Isaac Adatto, Dorothee Kling, Klaus Christensen, Elliot L. Chaikof, Roland Jakob-Roetne, Chad A. Cowan, Eduard Urich, Ludivine Challet-Meylan, Stephanie J. Grainger, Paul L. Huang, Per-Ola Freskgard, Yulei Xia, Tobias Heckel, Mary H.C. Florido, Christoph Patsch, Lin Sun, John F. O'Sullivan, Eva C. Thoma, Roberto Iacone |
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| Rok vydání: | 2015 |
| Předmět: |
Vascular Endothelial Growth Factor A
KOSR Time Factors Transcription Genetic Cellular differentiation Induced Pluripotent Stem Cells Myocytes Smooth Muscle Becaplermin Neovascularization Physiologic Bone Morphogenetic Protein 4 Mice SCID Biology Transfection Article Muscle Smooth Vascular Cell Line Glycogen Synthase Kinase 3 Mice Inbred NOD Human Umbilical Vein Endothelial Cells Animals Humans Metabolomics Cell Lineage Induced pluripotent stem cell Protein Kinase Inhibitors Wnt Signaling Pathway Induced stem cells Glycogen Synthase Kinase 3 beta Dose-Response Relationship Drug Gene Expression Profiling Endothelial Cells Gene Expression Regulation Developmental Cell Differentiation Proto-Oncogene Proteins c-sis Cell Biology Coculture Techniques Cell biology Endothelial stem cell Phenotype P19 cell Stem cell Biomarkers Adult stem cell |
| Zdroj: | Nature cell biology Nature Cell Biology |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb3205 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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