%0 Journal Article
%T Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells
%A Jason Tchao
%A Jong Jin Kim
%A Bo Lin
%A Guy Salama
%A Cecilia W. Lo
%A Lei Yang
%A Kimimasa Tobita
%J International Journal of Tissue Engineering
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/198762
%X During development, cardiac and skeletal muscle share major transcription factors and sarcomere proteins which were generally regarded as specific to either cardiac or skeletal muscle but not both in terminally differentiated adult cardiac or skeletal muscle. Here, we investigated whether artificial muscle constructed from human skeletal muscle derived stem cells (MDSCs) recapitulates developmental similarities between cardiac and skeletal muscle. We constructed 3-dimensional collagen-based engineered muscle tissue (EMT) using MDSCs (MDSC-EMT) and compared the biochemical and contractile properties with EMT using induced pluripotent stem (iPS) cell-derived cardiac cells (iPS-EMT). Both MDSC-EMT and iPS-EMT expressed cardiac specific troponins, fast skeletal muscle myosin heavy chain, and connexin-43 mimicking developing cardiac or skeletal muscle. At the transcriptional level, MDSC-EMT and iPS-EMT upregulated both cardiac and skeletal muscle-specific genes and expressed Nkx2.5 and Myo-D proteins. MDSC-EMT displayed intracellular calcium ion transients and responses to isoproterenol. Contractile force measurements of MDSC-EMT demonstrated functional properties of immature cardiac and skeletal muscle in both tissues. Results suggest that the EMT from MDSCs mimics developing cardiac and skeletal muscle and can serve as a useful in vitro functioning striated muscle model for investigation of stem cell differentiation and therapeutic options of MDSCs for cardiac repair. 1. Introduction The adult heart is largely a nonregenerative organ. Although cardiomyocytes (CMs), the contractile cells of the heart, have a modest rate of turnover, ranging from 1% in youth to less than 0.5% in old age [1], this level is not enough to compensate for the large number of cardiomyocytes which are lost as a result of heart injury. Combined with the fact that heart disease is the leading cause of death in the United States [2], this has prompted the search for novel therapies to replace damaged myocardium. Muscle derived stem cells (MDSCs) and induced pluripotent (iPS) stem cells are among the types of stem cells under investigation for cardiac repair. MDSCs are a multipotent, somatic stem cell which can be obtained from skeletal muscle via a modified preplate method [3]. MDSCs can be rapidly expanded in vitro to obtain clinically relevant numbers of cells, which can be transplanted as an autologous graft. They are also advantageous because they are resistant to hypoxia, attenuate fibrosis, and readily differentiate into contractile cells [4]. We previously showed that rodent
%U http://www.hindawi.com/journals/ijte/2013/198762/