Smooth-muscle-like cells derived from human embryonic stem cells support and augment cord-like structures in vitro.
Engineering vascularized tissue is crucial for its successful implantation, survival, and integration with the host tissue. Vascular smooth muscle cells (v-SMCs) provide physical support to the vasculature and aid in maintaining endothelial viability. In this study, we show an efficient derivation of v-SMCs from human embryonic stem cells (hESCs), and demonstrate their functionality and ability to support the vasculature in vitro. Human ESCs were differentiated in monolayers and supplemented with platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta 1 (TGF-beta1). Human ESC-derived smooth-muscle-like cells (SMLCs) were found to highly express specific smooth muscle cell (SMC) markers--including alpha-smooth muscle actin, calponin, SM22, and smooth muscle myosin heavy chain--to produce and secrete fibronectin and collagen, and to contract in response to carbachol. In vitro tubulogenesis assays revealed that these hESC-derived SMLCs interacted with human endothelial progenitor cell (EPCs) to form longer and thicker cord-like structures in vitro. We have demonstrated a simple protocol for the efficient derivation of highly purified SMLCs from hESCs. These in vitro functional SMLCs interacted with EPCs to support and augment capillary-like structures (CLSs), demonstrating the potential of hESCs as a cell source for therapeutic vascular tissue engineering.
Vo
Elaine
E
Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Science Oncology Center and Institute for NanoBioTechnology, The Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Hanjaya-Putra
Donny
D
Zha
Yuanting
Y
Kusuma
Sravanti
S
Gerecht
Sharon
S
D001808:Blood Vessels / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods