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Characterization of a Novel in Vitro Model for Smooth Muscle Differentiation
Author(s) -
Chen Shiyou,
Guo Xia
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1026.31
Subject(s) - calponin , microbiology and biotechnology , cellular differentiation , myosin , embryonic stem cell , biology , vascular smooth muscle , mesenchymal stem cell , serum response factor , myocardin , in vitro , transforming growth factor , myocyte , directed differentiation , chemistry , actin , gene expression , endocrinology , smooth muscle , gene , genetics , induced pluripotent stem cell
The objective of this study was to characterize a novel in vitro model for SMC differentiation from mesenchymal stem cells (huMSCs) derived from human embryonic stem cells. We found that huMSCs were differentiated into SMC phenotype by transforming growth factor‐β (TGF‐β) and retinoid acid (RA) in a dose‐ and time‐dependent manner, as demonstrated by the expression of SMC specific genes including smooth muscle α‐actin, SM22α, calponin, and smooth muscle myosin heavy chain. Both TGF‐β and RA induced huMSC to become an elongated, spindle‐shaped contractile morphology. Importantly, the SMCs differentiated from huMSC contracted in response to the stimulation of muscarinic agonist carbachol and KCl. Additional studies demonstrated that TGF‐β‐induced SMC differentiation from huMSC was SRF‐dependent because CArG box mutation diminished α‐SMA and SM22α promoter activities. Taken together, this simple and efficient cell model system is likely to serve as a valuable tool in understanding molecular mechanisms of human SMC differentiation during vascular development. It may also become a potential cell source for therapeutic application to treat vascular diseases. (Funding source: NIH R01HL093429)