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
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
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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