Targeting Muscle Regeneration with Small Extracellular Vesicles from Adipose Tissue-Derived Stem Cells-A Review.

Extracellular vesicles (EVs) are membrane-bound structures released by cells carrying diverse biomolecules involved in intercellular communication. Small EVs are abundant in body fluids, playing a key role in cell signaling. Their natural occurrence and therapeutic potential, especially in the context of muscular disorders, make them a significant area of research. Sarcopenia, characterized by progressive muscle fiber loss, represents a pathological state in which EVs could offer therapeutic benefits, reducing morbidity and mortality. Recent studies have proposed an interplay between adipose tissue (AT) and skeletal muscle regarding sarcopenia pathology. AT dysregulation, as seen in obesity, contributes to skeletal muscle loss in a multifactorial way. While AT-derived stem cell (ATDSC) small EVs have been implicated in musculoskeletal homeostasis, their precise action in muscle regeneration remains incompletely understood. In this context, ATDSC-derived small EVs can stimulate skeletal muscle regeneration through improved proliferation and migration of muscle cells, enhancement of muscular perfusion, improvement of tendon and nerve regeneration, stimulation of angiogenesis, and promotion of myogenic differentiation. However, they can also increase skeletal muscle loss. Notably, this is the first comprehensive review to systematically examine the role of ATDSC-derived small EVs in sarcopenia.