Human umbilical cord-derived mesenchymal stromal cells ameliorate aging-associated skeletal muscle atrophy and dysfunction by modulating apoptosis and mitochondrial damage in SAMP10 mice

Stem Cell Res Ther. 2022 Jun 3;13(1):226. doi: 10.1186/s13287-022-02895-z.

Abstract

Background: Skeletal muscle mass and function losses in aging individuals are associated with quality of life deterioration and disability. Mesenchymal stromal cells exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in aging-related degenerative disease.

Methods and results: We investigated the efficacy of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) on sarcopenia-related skeletal muscle atrophy and dysfunction in senescence-accelerated mouse prone 10 (SAMP10) mice. We randomly assigned 24-week-old male SAMP10 mice to a UC-MSC treatment group and control group. At 12 weeks post-injection, the UC-MSC treatment had ameliorated sarcopenia-related muscle changes in performance, morphological structures, and mitochondria biogenesis, and it enhanced the amounts of proteins or mRNAs for myosin heavy chain, phospho-AMP-activated protein kinase, phospho-mammalian target of rapamycin, phospho-extracellular signal-regulated kinase1/2, peroxisome proliferator-activated receptor-γ coactivator, GLUT-4, COX-IV, and hepatocyte growth factor in both gastrocnemius and soleus muscles, and it reduced the levels of proteins or mRNAs for cathepsin K, cleaved caspase-3/-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and gp91phox mRNAs. The UC-MSC treatment retarded mitochondria damage, cell apoptosis, and macrophage infiltrations, and it enhanced desmin/laminin expression and proliferating and CD34+/Integrin α7+ cells in both types of skeletal muscle of the SAMP10 mice. In vitro, we observed increased levels of HGF, PAX-7, and MoyD mRNAs at the 4th passage of UC-MSCs.

Conclusions: Our results suggest that UC-MSCs can improve sarcopenia-related skeletal muscle atrophy and dysfunction via anti-apoptosis, anti-inflammatory, and mitochondrial biogenesis mechanisms that might be mediated by an AMPK-PGC1-α axis, indicating that UC-MSCs may provide a promising treatment for sarcopenia/muscle diseases.

Keywords: Apoptosis; Inflammation; Mitochondria; SAMP10; Sarcopenia; Umbilical cord-derived mesenchymal stromal cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Apoptosis
  • Humans
  • Male
  • Mammals
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / pathology
  • Muscular Atrophy / therapy
  • Quality of Life
  • Sarcopenia* / metabolism
  • Sarcopenia* / pathology
  • Sarcopenia* / therapy
  • Umbilical Cord / metabolism