The synergistic effect of treadmill running on stem-cell transplantation to heal injured skeletal muscle.
Muscle-derived stem-cell (MDSC) transplantation presents a promising method for the treatment of muscle injuries. This study investigated the ability of exercise to enhance MDSC transplantation into the injured muscle. Mice were divided into four groups: contusion + phosphate-buffered saline (C + PBS; n = 14 muscles), C + MDSC transplantation (n = 12 muscles), C + PBS + treadmill running (C + PBS + TM; n = 17 muscles), and C + MDSC + TM (n = 13 muscles). One day after injury, the TM groups began running for 1 or 5 weeks. Two days after injury, muscles of C + MDSC and C + MDSC + TM groups were injected with MDSCs. One or 5 weeks later, the number and differentiation of transplanted MDSCs, myofiber regeneration, collagen I formation, and vascularity were assessed histologically. In vitro, MDSCs were subjected to mechanical stimulation, and growth kinetics were quantified. In vitro, mechanical stimulation decreased the MDSC population doubling time (18.6 +/- 1.6 h) and cell division time (10.9 +/- 0.7 h), compared with the controls (population doubling time: 23.0 +/- 3.4 h; cell division time: 13.3 +/- 1.1 h) (p = 0.01 and 0.03, respectively). In vivo, 5 weeks of TM increased the myogenic contribution of transplanted MDSCs, compared with the controls (p = 0.02). C + MDSC, C + PBS + TM, and C + MDSC + TM demonstrated decreased fibrosis at 5 weeks, compared with the C + PBS controls (p = 0.00, p = 0.03, and p = 0.02, respectively). Results suggest that the mechanical stimulation favors MDSC proliferation, both in vitro and in vivo, and that exercise enhances MDSC transplantation after injury.
Ambrosio
Fabrisia
F
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, USA. ambrosiof@upmc.edu
Ferrari
Ricardo J
RJ
Distefano
Giovanna
G
Plassmeyer
Joshua M
JM
Carvell
George E
GE
Deasy
Bridget M
BM
Boninger
Michael L
ML
Fitzgerald
G Kelley
GK
Huard
Johnny
J
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology*; D010805:Physical Conditioning, Animal; D012038:Regeneration; D033581:Stem Cell Transplantation; D014161:Transduction, Genetic; D014945:Wound Healing; D001616:beta-Galactosidase / Q000378:metabolism
D003094:Collagen; D001616:beta-Galactosidase