Table 4.

Therapeutic advantages of EVs released by hAF MSCs.

EVs’ Source	Diseases Model	In Vitro and/or In Vivo Experiments	Molecular Mechanism Proposed	Pathophysiological Effects	References
hAFMSC-derived EVs	Skeletal muscle atrophy	In vivo	Modulation of the expression of inflammatory (Il-1α, Il-6, and Il-4) and pro-resolving (Il-10) cytokines.	+ Muscle strength + Supporting long-term regeneration − Inflammation − Muscle degeneration	[109]
hAFMSC-derived EVs	Ischemic stroke	In vitro	Activation of the neurotrophic pathways BDNF/TrkB and the survival pathways PI3K/Akt and ERK5, as well as by the suppression of the death pathways (p75/JNK).	+ Cell survival + Neuronal plasticity + Neural replacement − Cognitive loss − Apoptosis − Inflammation − Oxidative stress	[110]
hAFMSC-derived EVs	Osteoarthritis	In vitro and in vivo	Increase in anti-inflammatory cytokines (e.g., IL-10) and decrease in pro-inflammatory cytokines (e.g., IL-1b, IL-6, TNF-α, and IL-12).	+ Cartilage repair + Cell proliferation + Cell migration + Cartilage matrix synthesis − Degeneration of cartilage	[111]
hAFMSC-derived EVs	Ischemic myocardial	In vitro and in vivo	Activation of intracellular Ca2+ signals and activation of downstream Ca2+-dependent processes.	+ Cardioprotection + Pro-angiogenic action + Proliferation − Apoptosis	[112,113]
hAFMSC-derived EVs	Cutaneous injury	In vivo	Inhibition of TGF-βR1 and TGF-βR2 expression.	+ Wound healing rate + Regeneration levels of hair follicles, nerves, and vessels + Natural distribution of collagen fibers − Fibroblast differentiation − Fibrotic scarring	[114]
hAFMSC-derived EVs	Necrotizing enterocolitis	In vitro and vivo	Activation of Wnt/β-catenin pathway signaling.	+ Cellular regeneration + Mitigating damage in intestinal tissue − Acting against intestinal injury − Mucosal inflammation	[115]
hAFMSC-derived EVs	Premature ovarian failure	In vitro and vivo	Negative modulation of cell apoptosis and positive regulation of cell survival.	+ Survival of granulosa cells + Apoptotic resistance	[116]