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Mesenchymal Stem Cells Augment the Adaptive Response to Eccentric Exercise

ZOU, KAI1,2; HUNTSMAN, HEATHER D.1,2; CARMEN VALERO, M.1,2; ADAMS, JOSEPH1,2; SKELTON, Jack1,2; DE LISIO, MICHAEL1,2; JENSEN, Tor3; BOPPART, MARNI D.1,2

Medicine & Science in Sports & Exercise: February 2015 - Volume 47 - Issue 2 - p 315–325
doi: 10.1249/MSS.0000000000000405
Basic Sciences

Purpose: The α7β1 integrin is a transmembrane protein expressed in the skeletal muscle that can link the actin cytoskeleton to the surrounding basal lamina. We have previously demonstrated that transgenic mice overexpressing the α7B integrin in the skeletal muscle (MCK:α7B; α7Tg) mount an enhanced satellite cell and growth response to single or multiple bouts of eccentric exercise. In addition, interstitial stem cells characterized as mesenchymal stem cells (MSCs) accumulate in α7Tg muscle (mMSCs) in the sedentary state and after exercise. The results from these studies prompted us to determine the extent to which mMSC underlie the beneficial adaptive responses observed in α7Tg skeletal muscle after exercise.

Methods: mMSCs (Sca-1+CD45) were isolated from α7Tg mice, dye-labeled, and intramuscularly injected into adult wild type recipient mice. After injection of mMSCs or saline, mice remained sedentary (SED) or were subjected to eccentric exercise training (TR) (downhill running) on a treadmill (three times per week) for 2 or 4 wk. Gastrocnemius–soleus complexes were collected 24 h after the last bout of exercise.

Results: mMSCs did not directly fuse with existing fibers; however, mMSCs injection enhanced Pax7+ satellite cell number and myonuclear content compared with all other groups at 2 wk after exercise. Mean CSA, percentage of larger caliber fibers (>3000 μm2), and grip strength were increased in mMSCs/TR compared with saline/SED and mMSCs/SED at 4 wk. mMSC transplantation did not enhance repair or growth in the absence of exercise.

Conclusions: The results from this study demonstrate that mMSCs contribute to beneficial changes in satellite cell expansion and growth in α7Tg muscle after eccentric exercise. Thus, MSCs that naturally accumulate in the muscle after eccentric contractions may enhance the adaptive response to exercise.

1Department of Kinesiology and Community Health, University of Illinois, Urbana, IL; 2Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, IL; and 3Division of Biomedical Sciences, University of Illinois, Urbana, IL

Address for correspondence: Marni D. Boppart, Sc.D., Beckman Institute for Advanced Science and Technology, 405 N. Mathews Avenue, MC-251 Urbana, IL 61801; E-mail: mboppart@illinois.edu.

Submitted for publication February 2014.

Accepted for publication May 2014.

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© 2015 American College of Sports Medicine