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Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dental pulp stem cells (DPSCs) have been proposed to replace the degenerated dopaminergic neurons due to its inherent neurogenic and regenerative potential. However, the effective delivery and homing of DPSCs within the lesioned brain has been one of the many obstacles faced in cell-based therapy of neurodegenerative disorders. We hypothesized that DPSCs, delivered intranasally, could circumvent these challenges. In the present study, we investigated the therapeutic efficacy of intranasally administered DPSCs in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Human deciduous DPSCs were cultured, pre-labelled with PKH 26, and intranasally delivered into PD mice following MPTP treatment. Behavioural analyses were performed to measure olfactory function and sensorimotor coordination, while tyrosine hydroxylase (TH) immunofluorescence was used to evaluate MPTP neurotoxicity in SNpc neurons. Upon intranasal delivery, degenerated TH-positive neurons were ameliorated, while deterioration in behavioural performances was significantly enhanced. Thus, the intranasal approach enriched cell delivery to the brain, optimizing its therapeutic potential through its efficacious delivery and protection against dopaminergic neuron degeneration.

Introduction: Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells (MSCs) derived from the connective tissue that resides within the dental pulp chamber. These cells originate from the neural crest lineage, exhibiting a strong neurodifferentiation profile and neuroprotective capacities. The neurotrophic factors such as Brain-Derived Neurotrophic Factor (BDNF) and Glial cell Derived Neurotrophic Factor (GDNF) are crucial for neuronal functional recovery and establishing new neuronal networks. In this study, we aim to explore the neurogenic potential of hDPSC and its therapeutic uses. Methods: hDPSCs were isolated from dental pulp tissue of extracted third molar using the enzymatic digestion method. hDPSCs were then propagated in culture media supplemented with a human serum substitute. Immunophenotyping and bi-lineage differentiation were carried out to characterize the isolated hDPSC. In addition, the neurotrophic factors secreted by hDPSC were analysed using a specific enzyme-linked immunosorbant assay (ELISA). Results: The hDPSCs were successfully isolated and expanded in vitro until passage 4. They exhibited fibroblast-like, spindle-shaped morphology in culture and showed high expression of MSC-specific surface markers (CD105, CD90, CD73 and CD29) and expressed relatively low levels of negative markers (CD45, CD14, CD34, CD79a and anti-HLA-DR). Besides that, isolated hDPSCs have shown the potential to differentiate into osteocytes and adipocytes. Furthermore, results from ELISA revealed that BDNF and GDNF were detected in high quantities. Conclusion: In this preliminary experiment, we have evaluated the neurotrophic factors secreted by hDPSCs in vitro culture. This study presents promising prospects in terms of the therapeutic potential of hDPSC in the prevention and treatment of neurological diseases. [ABSTRACT FROM AUTHOR]