Human umbilical cord-derived mesenchymal stromal cell exosomes ameliorate aging-associated skeletal muscle atrophy and dysfunction in SAMP10 mice.

BACKGROUND: Loss of skeletal muscle mass and function in aging individuals is closely linked to physical deterioration and disability. Because exosomes of human umbilical cord-derived mesenchymal stem cells (hucMSC-Exos) have been widely used to treat various human diseases, we examined their effects on aging-associated muscle atrophy and dysfunction in senescence-accelerated mouse prone 10 (SAMP10) mice, an animal model of human Sarcopenia. METHODS: Twenty-four-week-old male SAMP10 mice were randomly assigned to a non-treatment or hucMSC-Exos treatment group. RESULTS: Twelve weeks after intravenous injection of hucMSC-Exos, the treatment group mice showed improvements in skeletal muscle morphology and performance, and elevated levels of the proteins phospho-mammalian target of rapamycin (p-mTOR), myosin heavy chain (MHC), peroxisome proliferator-activated receptor-γ co-activator, and sirtuin1 (Sirt1) in gastrocnemius muscle tissues. HucMSC-Exos also improved muscle mitochondrial biogenesis and lipid drop accumulation in the gastrocnemius muscles. In in vitro experiments, hucMSC-Exos improved cell viability, senescence, apoptosis, and differentiation in association with induction of molecules related to anti-apoptosis (Bcl-2), differentiation (myogenin, MyoD1, myogenic factor-5, and myogenic factor-6), and protein anabolism (p-mTOR, MHC, Sirt1, phospho-AMP-activated protein kinase, phosphor-extracellular signal-regulated kinase1/2, and glycogen synthase kinase3alpha/beta) in C2C12 cells under our experimental conditions. CONCLUSIONS: Our findings indicate that hucMSC-Exos treatment ameliorated skeletal muscle atrophy and dysfunction via mitochondrial biogenesis, anti-apoptosis, and protein anabolism mechanisms that might be dependent on an mTOR and Sirt1/PGC1α signaling pathways, indicating that hucMSC-Exos may have promise as a treatment for the management of aging-related frailty and sarcopenia.