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

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.

Image-based crosstalk analysis of cell–cell interactions during sprouting angiogenesis using blood-vessel-on-a-chip

“…MPS can be used as a pharmacological assay and as a personalized prevalidation tool for various cell-based treatments, such as stem cell therapy [59][60][61]. As mentioned in the introduction, in the future, MPS may serve as a tool to support the decision-making of physicians or patients by presenting the success rate of stem cell transplantation or therapeutic angiogenesis.…”

Mitochondria Transplantation from Stem Cells for Mitigating Sarcopenia

“…Mitochondrial transplantation is deemed to a novel approach for the treatment of various forms of mitochondrial myopathy [19,22]. Many studies have suggested that the transfer of mitochondria from stem cells to damaged cells can improve energy metabolism, preserve mitochondrial function, and improve quality of life (Table 1) [39][40][41][42][43][44][45][46]. Mitochondrial DNA (mtDNA) deficiency or DNA mutations cause a gradual decline in mitochondrial function and sarcopeniarelated skeletal muscle atrophy.…”

miR-873-5p Suppression Reinvigorates Aging Mesenchymal Stem Cells and Improves Cardiac Repair after Myocardial Infarction

“…Additionally, our prior research has demonstrated that miR-873-5p mimics can impede AMPK phosphorylation . miR-873-5p is known to be involved in various signaling pathways. , The deceleration of MSC senescence has been linked to the activation of the AMPK signaling pathway. , The exploration of a suspected relationship between miR-873-5p and MSC aging is prompted by the observed alteration in miR-873-5p expression levels. Nevertheless, it remains uncertain whether or in what manner miR-873-5p influences the senescence of MSCs in the context of AMI.…”