SHED-derived small extracellular vesicles as potential neuro-immune modulators in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurological condition for which current therapeutic efficacy remains limited. This narrative review evaluates AD as a system-level biological disruption and proposes a mechanistic framework that utilises small extracellular vesicles (sEVs) derived from stem cells from human exfoliated deciduous teeth (SHEDs) as neuroimmune modulators of AD. HIGHLIGHT: Databases including PubMed, Scopus, and Web of Science were used to identify relevant studies. This search strategy primarily focused on SHED-derived extracellular vesicles (EVs) and their therapeutic relevance in AD. Preclinical in vivo and in vitro studies investigating SHEDs or SHED-derived EVs in a neurological context were examined. SHED-derived EVs exhibited neurotrophic, immunomodulatory, and metabolic regulatory properties in preclinical models. Heterogeneity in the study design and the absence of direct AD validation preclude conclusions regarding their efficacy as a therapeutic strategy for AD. However, the effects of SHED-derived sEVs have shown consistent features across various neurodegenerative disease models, suggesting that their therapeutic relevance is underexplored. Broader evidence from mesenchymal stem cell (MSC)-derived sEVs in AD transgenic models provides a mechanistic foundation for this research gap. With specific microRNA loading, SHED-derived sEVs may modulate AD-relevant pathological pathways. CONCLUSION: Good Manufacturing Practice-compliant SHED expansion, standardised EV isolation, careful dose evaluation, and effective delivery systems are essential for advancing SHED-derived EV strategies. However, direct validation of SHED-derived sEVs in AD-specific in vivo models remains necessary. Therefore, the current findings should be viewed as a mechanistic roadmap for future research rather than as evidence of therapeutic efficacy.