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Neuromuscular Electrical Stimulation as a Method to Maximize the Beneficial Effects of Muscle Stem Cells Transplanted into Dystrophic Skeletal Muscle

Distefano, G and Ferrari, RJ and Weiss, C and Deasy, BM and Boninger, ML and Fitzgerald, GK and Huard, J and Ambrosio, F (2013) Neuromuscular Electrical Stimulation as a Method to Maximize the Beneficial Effects of Muscle Stem Cells Transplanted into Dystrophic Skeletal Muscle. PLoS ONE, 8 (3).

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Cellular therapy is a potential approach to improve the regenerative capacity of damaged or diseased skeletal muscle. However, its clinical use has often been limited by impaired donor cell survival, proliferation and differentiation following transplantation. Additionally, functional improvements after transplantation are all-too-often negligible. Because the host microenvironment plays an important role in the fate of transplanted cells, methods to modulate the microenvironment and guide donor cell behavior are warranted. The purpose of this study was to investigate whether the use of neuromuscular electrical stimulation (NMES) for 1 or 4 weeks following muscle-derived stem cell (MDSC) transplantation into dystrophic skeletal muscle can modulate the fate of donor cells and enhance their contribution to muscle regeneration and functional improvements. Animals submitted to 4 weeks of NMES after transplantation demonstrated a 2-fold increase in the number of dystrophin+ myofibers as compared to control transplanted muscles. These findings were concomitant with an increased vascularity in the MDSC+NMES group when compared to non-stimulated counterparts. Additionally, animals subjected to NMES (with or without MDSC transplantation) presented an increased maximal specific tetanic force when compared to controls. Although cell transplantation and/or the use of NMES resulted in no changes in fatigue resistance, the combination of both MDSC transplantation and NMES resulted in a faster recovery from fatigue, when compared to non-injected and non-stimulated counterparts. We conclude that NMES is a viable method to improve MDSC engraftment, enhance dystrophic muscle strength, and, in combination with MDSC transplantation, improve recovery from fatigue. These findings suggest that NMES may be a clinically-relevant adjunct approach for cell transplantation into skeletal muscle. © 2013 Distefano et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Distefano, Ggid7@pitt.eduGID7
Ferrari, RJRJF67@pitt.eduRJF67
Weiss, Ccmw50@pitt.eduCMW50
Deasy, BM
Boninger, MLboninger@pitt.eduBONINGER0000-0001-6966-919X
Fitzgerald, GKkfitzger@pitt.eduKFITZGER0000-0001-6293-3103
Huard, J
Ambrosio, Ffaa7@pitt.eduFAA7
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Date: 19 March 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0054922
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Orthopaedic Surgery
School of Medicine > Physical Medicine and Rehabilitation
Refereed: Yes
Date Deposited: 08 Apr 2013 17:11
Last Modified: 14 May 2024 11:55


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