Abstract

BACKGROUND: Muscle atrophy due to disuse occurs along with adverse physiological and functional changes, but bone marrow stromal cells (MSCs) may be able to act as muscle satellite cells to restore myofibers. Thus, we investigated whether MSCs could enhance the proliferation of satellite cells and suppress myonuclear apoptosis during immobilization.

MATERIAL AND METHODS: We isolated, purified, amplified, and identified MSCs. Rats (n=48) were randomized into 3 groups: WB group (n=16), IM-PBS group (n=16), and IM-MSC (n=16). Rat hind limbs were immobilized for 14 d, treated with MSCs or phosphate-buffered saline (PBS), and then studied using immunohistochemistry and Western blot analysis to characterize the proteins involved. Apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-UTP nick end labeling (TUNEL) method.

RESULTS: We compared muscle mass, cross-sectional areas, and peak tetanic forces and noted insignificant differences between PBS- and MSC-treated animals, but satellite cell proliferation was significantly greater after MSC treatment (p<0.05). Apoptotic myonuclei were reduced (p<0.05) after MSC treatment as well. Pro-apoptotic Bax was down-regulated and anti-apoptotic Bcl-2 and p-Akt protein were upregulated (p<0.05).

CONCLUSIONS: MSCs injected during hind limb immobilization can maintain satellite cell activity by suppressing myonuclear apoptosis.

Keywords: Cell Proliferation - physiology, Cell Differentiation - physiology, Apoptosis - physiology, Immobilization, Mesenchymal Stem Cell Transplantation - methods, Mesenchymal Stromal Cells - physiology, Muscular Atrophy - therapy, Random Allocation, Rats, Wistar, Satellite Cells, Skeletal Muscle - physiology