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Functional Overloading of Dystrophic Mice Enhances Muscle-Derived Stem Cell Contribution to Muscle Contractile Capacity

Ambrosio, F and Ferrari, RJ and Fitzgerald, GK and Carvell, G and Boninger, ML and Huard, J (2009) Functional Overloading of Dystrophic Mice Enhances Muscle-Derived Stem Cell Contribution to Muscle Contractile Capacity. Archives of Physical Medicine and Rehabilitation, 90 (1). 66 - 73. ISSN 0003-9993

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Abstract

Ambrosio F, Ferrari RJ, Fitzgerald GK, Carvell G, Boninger ML, Huard J. Functional overloading of dystrophic mice enhances muscle-derived stem cell contribution to muscle contractile capacity. Arch Phys Med Rehabil. Objectives: To evaluate the effect of functional overloading on the transplantation of muscle derived stem cells (MDSCs) into dystrophic muscle and the ability of transplanted cells to increase dystrophic muscle's ability to resist overloading-induced weakness. Design: Cross-sectional. Setting: Laboratory. Animals: Male mice (N=10) with a dystrophin gene mutation. Interventions: MDSCs were intramuscularly transplanted into the extensor digitorum longus muscle (EDL). Functional overloading of the EDL was performed by surgical ablation of the EDL's synergist. Main Outcome Measures: The total number of dystrophin-positive fibers/cross-section (as a measure of stem cell engraftment), the average number of CD31+ cells (as a measure of capillarity), and in vitro EDL contractile strength. Independent t tests were used to investigate the effect of overloading on engraftment, capillarity, and strength. Paired t tests were used to investigate the effect of MDSC engraftment on strength and capillarity. Results: MDSC transplantation protects dystrophic muscles against overloading-induced weakness (specific twitch force: control 4.5N/cm2±2.3; MDSC treated 7.9N/cm2±1.4) (P=.02). This improved force production following overloading is concomitant with an increased regeneration by transplanted MDSCs (MDSC: 26.6±20.2 dystrophin-positive fibers/cross-section; overloading + MDSC: 170.6±130.9 dystrophin-positive fibers/cross-section [P=.03]). Overloading-induced increases in skeletal muscle capillarity is significantly correlated with increased MDSC engraftment (R2=.80, P=.01). Conclusions: These findings suggest that the functional contribution of transplanted MDSCs may rely on activity-dependent mechanisms, possibly mediated by skeletal muscle vascularity. Rehabilitation modalities may play an important role in the development of stem cell transplantation strategies for the treatment of muscular dystrophy. © 2009 American Congress of Rehabilitation Medicine.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ambrosio, Ffaa7@pitt.eduFAA7
Ferrari, RJRJF67@pitt.eduRJF67
Fitzgerald, GKkfitzger@pitt.eduKFITZGER0000-0001-6293-3103
Carvell, Ggcarvell@pitt.eduGCARVELL
Boninger, MLboninger@pitt.eduBONINGER
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 January 2009
Date Type: Publication
Journal or Publication Title: Archives of Physical Medicine and Rehabilitation
Volume: 90
Number: 1
Page Range: 66 - 73
DOI or Unique Handle: 10.1016/j.apmr.2008.06.035
Schools and Programs: School of Health and Rehabilitation Sciences > Rehabilitation Science
School of Medicine > Orthopaedic Surgery
Refereed: Yes
ISSN: 0003-9993
MeSH Headings: Animals; Cells, Cultured; Disease Models, Animal; Dystrophin--administration & dosage; Dystrophin--deficiency; Dystrophin--pharmacology; Male; Mice; Muscle Contraction--physiology; Muscle Fibers, Skeletal--drug effects; Muscular Dystrophy, Animal--therapy; Stem Cell Transplantation
PubMed ID: 19154831
Date Deposited: 09 Apr 2014 16:33
Last Modified: 22 Jun 2021 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/21053

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