This review summarizes hDPSCs' ability to differentiate into neuronal cell types, provide paracrine neuroprotection, and be combined with biomaterial scaffolds, with preclinical evidence across CNS/PNS injuries including Parkinson's disease.

It highlights a promising cell-based regenerative approach that could inform PD neuroprotection/transplant strategies, but as a broad preclinical review lacking PD-specific mechanistic targets or actionable translational data its immediate value for Parkinson's drug discovery is modest.

Neural injuries affecting both the central nervous system (CNS) and peripheral nervous system (PNS) pose a great clinical challenge due to the neural tissue's limited self-regenerative capacity. Human dental pulp stem cells (hDPSCs), derived from the neural crest and easily obtained from extracted teeth, exhibit considerable potential for neural regeneration. This potential is attributed to their ability to directly differentiate into various neuronal cell types, paracrine effects, and interactions with biomaterial scaffolds. In this review, we reviewed the molecular mechanisms by which hDPSCs support neural repair, highlighting their direct neuronal differentiation function, neuroprotection function via paracrine signaling, and recent innovations in biomaterial scaffolds that enhance the viability of hDPSCs for neuroregenerative applications. Preclinical studies have shown promising therapeutic effects of hDPSCs in spinal cord injuries (SCI), strokes, Parkinson's disease (PD), Alzheimer's disease (AD), and peripheral nerve injuries. However, challenges remain, including optimizing neuronal differentiation specificity, ensuring immunological safety, and achieving scalable clinical applications. Future research should focus on standardizing manufacturing protocols, implementing strict quality control, and developing functional assays linked to neural recovery to maximize the potential of hDPSCs for nervous system regeneration.