Mesenchymal Stem Cells Suppress Muscle Atrophy Induced by Hindlimb Suspension

Abstract

Objective: The protective effects of human mesenchymal stem cells (MSCs) isolated from different sources (bone marrow, adipose tissue and umbilical cord) on skeletal muscle regeneration were investigated using a hindlimb suspension (HS)-induced muscle atrophy rodent model. Methods: Female SD rats were randomly assigned to three groups: control, hindlimb suspension (HS), and hindlimb suspension and reloaded (HR). After induction of muscle atrophy for two weeks, MSCs (1 x 106 cells) were injected into the soleus muscle in the HS and HR groups. Two weeks later, the changes of muscle mass, crosssectional area (CSA), muscle-specific gene expression, lactate accumulation and muscle atrophy signaling pathwayrelated proteins were compared. Results: In the MSCs-injected groups, there was an increase in soleus muscle mass, CSA and expression of skeletal muscle actin and desmin, as well as a decrease in lactate accumulation. All MSCs play an effective role in improvement of the muscle state from the muscle atrophy condition. Especially, HR groups accompanied by normal activity after MSCs injection showed synergic effect on recovery of atrophic muscle. Furthermore, treatment with the MSCs activated the PI3K/AKT pathway known as major signaling of muscle atrophy, consequently reducing expression of the muscle-specific RING finger protein-1 (MuRF-1) and atrophy F-box (MAFbx/Atrogin-1). Conclusions: The results can serve as fundamental data toward the development of new medical strategies for the rapid rehabilitation and regeneration of atrophied muscles.