title: Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells.
abstract: 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 usefulin vitrofunctioning striated muscle model for investigation of stem cell differentiation and therapeutic options of MDSCs for cardiac repair.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Tchao
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA ; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA ; McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Guy
authors.initials: G
authors.lastname: Salama
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA ; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15224, USA ; McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA ; Rangos Research Center, Room 8121, 4401 Pennsylvania Avenue, Pittsburgh, PA 15224, USA.
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
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