Abstract
BackgroundNeural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment.MethodsIn this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr1 gene were transplanted into the striatum of the rat model of PD. The results were evaluated through reverse transcription polymerase chain reaction (RT‐PCR), Western blot, and immunofluorescence analysis.ResultsThe behavioral abnormalities of PD rats were improved by combined transplantation of NSCs and microglia, both forced with Nurr1. The number of tyrosine hydroxylase+ cells in the striatum of PD rats increased, and the number of Iba1+ cells decreased compared with the other groups. Moreover, the dopamine neurons differentiated from grafted NSCs could still be detected in the striatum of PD rats after 5 months.ConclusionsThe results suggested that transplantation of Nurr1‐overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be a new potential strategy for the cell replacement therapy in PD.
Highlights
Parkinson's disease (PD) is a common neurodegenerative disease prevalent in older persons
Previous studies have shown that the microglia ac‐ tivation and the associated inflammatory changes are considered as major pathogenic contributors to PD.[9,10,11]
The results suggested that the overexpression of Nurr[1] improved the behav‐ ioral deficits of PD rats and increased the level of striatal DA neu‐ rons by promoting the differentiation of Neural stem cells (NSCs) into dopaminergic neurons and modulating toxic environments surrounding these neurons
Summary
Parkinson's disease (PD) is a common neurodegenerative disease prevalent in older persons. One concern is that most in vivo transplanted NSCs are differentiated into glial cells rather than neu‐ rons Another challenge is that only 5%‐10% of the NSCs survive after transplantation due to the toxic effect of the inflammatory environment.[8] Previous studies have shown that the microglia ac‐ tivation and the associated inflammatory changes are considered as major pathogenic contributors to PD.[9,10,11] Microglia can produce both pro‐inflammatory and neurotrophic cytokines in the central nervous system.[12,13] a strategy biased toward beneficial microglia could be a promising therapeutic approach in PD. Methods: In this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr[1] gene were transplanted into the striatum of the rat model of PD. Conclusions: The results suggested that transplantation of Nurr1‐overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be a new potential strategy for the cell replacement therapy in PD
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