Therapeutic potential of third molar-derived dental pulp stem cells in Alzheimer’s disease: Current evidence and future directions

Abstract

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by amyloid-β deposition, tau hyperphosphorylation, neuroinflammation, and progressive neuronal loss, with no curative therapy currently available. Dental pulp stem cells (DPSCs) derived from third molars represent an ethically accessible, minimally invasive, neural crest–derived mesenchymal stem cell source with self-renewal and multi-lineage differentiation potential. Preclinical evidence suggests that DPSCs exert neuroprotective effects by reducing oxidative stress and apoptosis, enhancing neurogenesis through synaptic repair and neuronal differentiation, and modulating neuroinflammation via microglial regulation. Their secretion of neurotrophic factors, including BDNF, GDNF, NGF, NT-3, CNTF, and HGF, further supports neuronal survival and functional recovery in Alzheimer’s disease models. Advances in 3D neurosphere and brain organoid models demonstrate the integration of DPSCs into neural circuitry, highlighting their translational potential. Nevertheless, challenges such as cell survival, migration, and functional integration within the diseased brain remain. Importantly, the use of extracted third molars avoids major ethical concerns associated with embryonic stem cells, making DPSCs a clinically relevant candidate for regenerative approaches. Future directions emphasize the development of exosome-based therapies, bioengineered scaffolds, gene-modified DPSC strategies, and personalized autologous interventions. Collectively, current evidence positions third molar–derived DPSCs as a promising avenue for disease-modifying and regenerative therapies in Alzheimer’s disease.