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

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.

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.

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.