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Updated: Jun 26, 2026
Transplantation of Induced Pluripotent Stem Cell-derived Mesoangioblast-like Myogenic Progenitors in Mouse Models of Muscle Regeneration
Published on: January 20, 2014
Functional overloading of dystrophic mice enhances muscle-derived stem cell contribution to muscle contractile
Fabrisia Ambrosio1, Ricardo J Ferrari, G Kelley Fitzgerald
1Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, USA. ambrosiof@upmc.edu
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.
