Combined biophysical and soluble factor modulation induces cardiomyocyte differentiation from human muscle derived stem cells. Sci Rep 2014 Oct 14;4:6614
Date
10/15/2014Pubmed ID
25310989Pubmed Central ID
PMC4196107DOI
10.1038/srep06614Scopus ID
2-s2.0-84946867263 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
Author List
Tchao J, Han L, Lin B, Yang L, Tobita KAuthor
Lu Han PhD Assistant Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biophysical PhenomenaCell Aggregation
Cell Differentiation
Gene Expression Regulation, Developmental
Humans
Muscle, Skeletal
Myocytes, Cardiac
Stem Cells
Transcription Factors
