Table of Contents
International Journal of Tissue Engineering
Volume 2013, Article ID 198762, 15 pages
http://dx.doi.org/10.1155/2013/198762
Research Article

Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells

1Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA
2Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
3Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA
4Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15224, USA
5McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
6Rangos Research Center, Room 8121, 4401 Pennsylvania Avenue, Pittsburgh, PA 15224, USA

Received 30 May 2013; Revised 19 September 2013; Accepted 28 September 2013

Academic Editor: Tianqing Liu

Copyright © 2013 Jason Tchao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 useful in vitro functioning striated muscle model for investigation of stem cell differentiation and therapeutic options of MDSCs for cardiac repair.