Umbilical cord mesenchymal stromal cells in sarcopenia: benefits and strategies for enhancing efficacy.

Sarcopenia is a progressive age-related condition characterized by the decline of skeletal muscle mass and function. Its development involves multiple cellular and molecular mechanisms, including chronic inflammation, apoptosis, mitochondrial dysfunction, and impaired muscle regeneration. Human umbilical cord mesenchymal stromal cells (HUC-MSCs) have emerged as a promising therapeutic strategy due to their potent immunomodulatory properties, paracrine effects, and ability to promote tissue repair. The regenerative potential of HUC-MSCs is largely mediated by the secretion of bioactive factors that suppress apoptosis, attenuate inflammation, enhance angiogenesis, and remodel the extracellular matrix, thereby establishing a microenvironment conducive to muscle regeneration. Nevertheless, challenges such as limited cell survival, differentiation efficiency, and long-term integration within host muscle, as well as variability in cell sources, delivery routes, and host immune responses, continue to constrain their clinical translation. In this review, we systematically summarize the biological characteristics of HUC-MSCs, their interactions with inflammatory and catabolic pathways in atrophic muscle, and their regulation of key signaling mechanisms involved in muscle repair. We also discuss current limitations and highlight future strategies-such as cellular preconditioning, biomaterial-assisted delivery systems, optimized transplantation protocols, and emerging organ-on-a-chip technologies-to enhance therapeutic efficacy and accelerate clinical application.