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Aging is characterized by measurable reductions in tissue repair, immune balance, and metabolic regulation. Increasing evidence suggests that these changes may arise, in part, from an insufficiency or altered quality of endogenous extracellular vesicle (EV) signaling. EVs, including exosomes, carry regenerative and immunoregulatory cues, and age-related alterations in their abundance, cargo, and bioactivity have been linked to impaired cellular communication across organ systems. This has fueled growing interest in stem cell-derived EVs, which provide biologically more youthful vesicles that reproduce key paracrine functions of their parent cells while avoiding the limitations of cell transplantation. By transferring defined protein, lipid, and RNA cargoes, these vesicles influence pathways central to aging biology, including mitochondrial function, inflammatory control, and maintenance of stem cell niches. Preclinical studies support their efficacy in models of neurodegeneration, wound healing, musculoskeletal decline, and systemic inflammation. However, their function depends on stem cell origin, donor age, and environmental conditioning, variables that complicate standardization and clinical scalability. As interest expands across therapeutic and cosmetic domains, a comparative understanding of EV sources and their mechanistic actions is required. In this review, we examine stem cell-derived EVs across biological sources, outline how aging and environmental factors shape their regenerative potency, and evaluate current progress in clinical translation. The field has reached a point where future advances depend less on further demonstrations of efficacy and more on resolving challenges related to manufacturing, quality control, and regulatory alignment. Addressing these constraints will determine whether stem cell-derived EVs can progress from experimental promise to practical interventions for aging and regenerative medicine.

More information Original publication

DOI

10.3389/fragi.2026.1752530

Type

Journal article

Publisher

Frontiers Media SA

Publication Date

2026-04-30T00:00:00+00:00

Volume

7