Dopamine (DA) cell replacement therapy in Parkinson’s disease (PD) can be achieved using human fetal mesencephalic tissue, however, limited tissue availability has hindered further developments. Alternatively, replacement of damaged DA neurons with their fusion with adult stem cells after bone marrow stem cells (BMSCs) transplantation is an attractive possible route to the restoration of neurological functions in PD. Fusion of BMSCs with somatic cells may account for some of the findings of BMSCs-neuronal differentiation. In addition, the periodic activation of the Wnt/β-catenin signalling in embryonic stem cells remarkably enhances cell fusion-mediated reprogramming of different somatic cells in vitro. Thus, in this research proposal, the main goal is to determine whether cell fusion-mediated reprogramming it occurs in vivo. Our hypothesis is that activation of the Wnt/β-catenin pathway is crucial to enhance reprogramming of fused cells and may rescue injured DA neuron cells in PD. Thereby, we will transplant perturbed (Wnt-activated) hematopoietic stem cells (HSCs) into mice suffering from experimental PD. Then, we will determine whether Wnt/β-catenin signalling controls and enhances in vivo reprogramming of hybrids formed in response to the neurodegenerative process. Furthermore, we will verify if Wnt-mediated reprogramming after HSCs fusion can repair the injured tissue. Accordingly, genetic approaches will be used to evaluate cell fusion and reprogramming events in the tissues analyzed. Short- and long-term regeneration will be also studied. In conclusion, cell fusion-mediated reprogramming mechanism could lead to the development of radical new therapy for Parkinson’s disease that currently lack effective treatment.
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