EFFECTS OF INFUSION OF DENTAL PULP-DERIVED MESENCHYMAL STEM CELLS INDUCED AND NOT INDUCED TO NEURONAL DIFFERENTIATION IN AN ANIMAL MODEL OF PARKINSON‘S DISEASE

Abstract

Background Parkinson‘s disease (PD) is a chronic neurodegenerative disease that typically affects dopaminergic neurons in the substantia nigra pars compacta (SNpc). Current therapy has several adverse effects, reinforcing the search for adjuvant therapeutic protocols such as stem cells. The use of mesenchymal stem cells (MSC) can promote a neuroprotective effect. However, information regarding their effectiveness and mechanisms of action in PD are lacking. Dental pulp stem cells (DPSC) have the potential to differentiate into neurons, expressing the genes of this cell type. This study aimed to evaluate the effects of infusion of induced and non-induced DPSC on neuronal differentiation in an animal model of PD induced by 6-hydroxydopamine (6-OHDA). Methods Third molars were collected, and DPSC were isolated and characterized according to the International Society for Cellular Therapy (ISCT). DPSC were induced to neuronal differentiation for 21 days. The differentiation potential was evaluated by immunofluorescence and immunophenotyping. For the animal model of PD, 6-OHDA (3µ in saline with 0.2% ascorbic acid) or saline with 0.2% ascorbic acid (1uL) was infused in the medial prosencephalic bundle of male Wistar rats (280-330g) to generate a retrograde lesion in the SNpc. The following groups were performed: SHAM, 6-OHDA+saline, 6-OHDA+DPSC, and 6-OHDA+DPSC induced to neuronal differentiation. After seven days, 100,000 cells were transplanted into the SNpc. An open field test was performed for the motor behavioral assessment. Results DPSC showed MSC characteristics according to an ISCT. The DPSC showed an immunophenotypic profile like neural stem cells regarding neuronal markers. After differentiation, there was an increase in the expression of βIII-tubulin (p Conclusion The animal model used showed significant motor impairment, which is characteristic of PD, and the infusion of induced and non-induced DPSC to neuronal differentiation proved to be efficient in reversing this impairment, demonstrating to be a promising strategy for the treatment of PD.