title: Concurrent generation of functional smooth muscle and endothelial cells via a vascular progenitor.
abstract: Smooth muscle cells (SMCs) and endothelial cells (ECs) are typically derived separately, with low efficiencies, from human pluripotent stem cells (hPSCs). The concurrent generation of these cell types might lead to potential applications in regenerative medicine to model, elucidate, and eventually treat vascular diseases. Here we report a robust two-step protocol that can be used to simultaneously generate large numbers of functional SMCs and ECs from a common proliferative vascular progenitor population via a two-dimensional culture system. We show here that coculturing hPSCs with OP9 cells in media supplemented with vascular endothelial growth factor, basic fibroblast growth factor, and bone morphogenetic protein 4 yields a higher percentage of CD31(+)CD34(+) cells on day 8 of differentiation. Upon exposure to endothelial differentiation media and SM differentiation media, these vascular progenitors were able to differentiate and mature into functional endothelial cells and smooth muscle cells, respectively. Furthermore, we were able to expand the intermediate population more than a billion fold to generate sufficient numbers of ECs and SMCs in parallel for potential therapeutic transplantations.
authors: Institute for Stem Cell Biology and Regenerative Medicine, Department of Obstetrics and Gynecology, Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, and Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors: Melanie
authors: M
authors: Marchand
authors: Erica K
authors: EK
authors: Anderson
authors: Smruti M
authors: SM
authors: Phadnis
authors: Michael T
authors: MT
authors: Longaker
authors: John P
authors: JP
authors: Cooke
authors: Bertha
authors: B
authors: Chen
authors: Renee A
authors: RA
authors: Reijo Pera
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology*; D061252:Feeder Cells; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D018919:Neovascularization, Physiologic; D039904:Pluripotent Stem Cells / Q000166:cytology*; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*
keywords: Embryonic stem cells; Endothelial cells; Smooth muscle cells; Stem cell