Abstract / Summary
Alzheimer’s disease (AD) affects more than 55 million people worldwide, and current pharmacological treatments provide only modest symptomatic benefits with limited effects on disease progression. Stem cell-based therapies, including mesenchymal stem cells (MSCs), neural stem cells (NSCs), induced pluripotent stem cell (iPSC)-derived products, and their extracellular vesicles (EVs), have emerged as potential regenerative strategies and have demonstrated encouraging results in preclinical models. Experimental studies suggest that these approaches may modulate neuroinflammation, oxidative stress, apoptosis, neurogenesis, and synaptic plasticity through multiple complementary mechanisms. Among these modalities, EVs have attracted increasing attention because of their lower immunogenicity, reduced tumorigenic risk, and potential to cross the blood–brain barrier (BBB). However, clinical evidence remains limited, with published trials primarily evaluating safety and feasibility rather than therapeutic efficacy. Major translational challenges, including limited brain delivery, manufacturing standardization, product characterization, and long-term safety, continue to impede clinical application. This review summarizes current mechanistic evidence for stem cell- and EV-based therapies in AD, critically discusses their translational limitations, and highlights future research priorities to support clinical development.