Cargando…

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

The use of human pluripotent stem cells for in vitro disease modeling 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 mus...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566857/
https://www.ncbi.nlm.nih.gov/pubmed/26214132
http://dx.doi.org/10.1038/ncb3205
Descripción
Sumario:The use of human pluripotent stem cells for in vitro disease modeling 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 or PDGF-BB resulted in the differentiation of either endothelial or vascular smooth muscle cells, respectively. Both protocols produced mature cells with efficiencies over 80% within six days. Upon 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.