title: Transdifferentiation of human endothelial progenitors into smooth muscle cells.
abstract: Access to smooth muscle cells (SMC) would create opportunities for tissue engineering, drug testing, and disease modeling. Herein we report the direct conversion of human endothelial progenitor cells (EPC) to induced smooth muscle cells (iSMC) by induced expression of MYOCD. The EPC undergo a cytoskeletal rearrangement resembling that of mesenchymal cells within 3 days post initiation of MYOCD expression. By day 7, the reprogrammed cells show upregulation of smooth muscle markers ACTA2, MYH11, and TAGLN by qRT-PCR and ACTA2 and MYH11 expression by immunofluorescence. By two weeks, they resemble umbilical artery SMC in microarray gene expression analysis. The iSMC, in contrast to EPC control, show calcium transients in response to phenylephrine stimulation and a contractility an order of magnitude higher than that of EPC as determined by traction force microscopy. Tissue-engineered blood vessels constructed using iSMC show functionality with respect to flow- and drug-mediated vasodilation and vasoconstriction.
authors.affiliation: Department of Biomedical Engineering, Columbia University, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, 10027, USA.
authors.forename: HaYeun
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC, 27708, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Atchison
authors.affiliation: Department of Biomedical Engineering, Columbia University, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, 10027, USA.
authors.forename: Zaozao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Columbia University, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, 10027, USA.
authors.forename: Syandan
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC, 27708, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Truskey
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC, 27708, USA.|Department of Biomedical Engineering, Khalifa University, P. O. Box 127788, Abu Dhabi, UAE.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Christoforou
authors.affiliation: Department of Biomedical Engineering, Columbia University, Mail Code 8904, 1210 Amsterdam Avenue, New York, NY, 10027, USA.
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D054338:Cell Transdifferentiation; D015536:Down-Regulation; D000071063:Endoglin / Q000235:genetics / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D018014:Gene Transfer Techniques; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D023822:Tissue Engineering; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000099152:Cadherin 5; D000099251:Myocardin
chemical_list: D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D000071063:Endoglin; D008840:Microfilament Proteins; D009124:Muscle Proteins; D018995:Myosin Heavy Chains; D009687:Nuclear Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015534:Trans-Activators; D000099152:Cadherin 5; D000099251:Myocardin; C541116:ACTA2 protein, human; C064206:ENG protein, human; C509903:MYH11 protein, human; C051615:transgelin
keywords: Direct reprogramming; Direct transdifferentiation; Myocardin; Smooth muscle cell differentiation; Tissue-engineered blood vessel