title: Combined biophysical and soluble factor modulation induces cardiomyocyte differentiation from human muscle derived stem cells.
abstract: Cellular cardiomyoplasty has emerged as a novel therapy to restore contractile function of injured failing myocardium. Human multipotent muscle derived stem cells (MDSC) can be a potential abundant, autologous cell source for cardiac repair. However, robust conditions for cardiomyocyte (CM) differentiation are not well established for this cell type. We have developed a new method for CM differentiation from human MDSC that combines 3-dimensional artificial muscle tissue (AMT) culture with temporally controlled biophysical cell aggregation and delivery of 4 soluble factors (microRNA-206 inhibitor, IWR-1, Lithium Chloride, and BMP-4) (4F-AG-AMT). The 4F-AG-AMT displayed cardiac-like response to β-adrenergic stimulation and contractile properties. 4F-AG-AMT expressed major cardiac (NKX2-5, GATA4, TBX5, MEF2C) transcription factors and structural proteins. They also express cardiac gap-junction protein, connexin-43, similar to CMs and synchronized spontaneous calcium transients. These results highlight the importance of temporal control of biophysical and soluble factors for CM differentiation from MDSCs.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Tchao
authors.affiliation: Developmental Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.affiliation: Developmental Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Developmental Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: 1] Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA [2] Developmental Biology, University of Pittsburgh, Pittsburgh, PA, USA [3] McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
mesh_terms: D055592:Biophysical Phenomena; D002449:Cell Aggregation; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D014157:Transcription Factors