Peripheral Delivery of Neural Precursor Cells Ameliorates Parkinson's Disease-Associated Pathology.

Edwards Iii Edwards Iii,Schulz Schulz,Gamez Gamez,Armijo Armijo,Soto Soto,Morales Morales,Moreno-Gonzalez Moreno-Gonzalez,Kramm Kramm,Taylor-Presse Taylor-Presse

doi:10.3390/cells8111359

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of motor control due to a wide loss of dopaminergic neurons along the nigro-striatal pathway. Some of the mechanisms that contribute to this cell death are inflammation, oxidative stress, and misfolded alpha-synuclein-induced toxicity. Current treatments are effective at managing the early motor symptoms of the disease, but they become ineffective over time and lead to adverse effects. Previous research using intracerebral stem cell therapy for treatment of PD has provided promising results; however, this method is very invasive and is often associated with unacceptable side effects. In this study, we used an MPTP-injected mouse model of PD and intravenously administered neural precursors (NPs) obtained from mouse embryonic and mesenchymal stem cells. Clinical signs and neuropathology were assessed. Female mice treated with NPs had improved motor function and reduction in the neuroinflammatory response. In terms of safety, there were no tumorigenic formations or any detectable adverse effect after treatment. Our results suggest that peripheral administration of stem cell-derived NPs may be a promising and safe therapy for the recovery of impaired motor function and amelioration of brain pathology in PD.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disease
PD is a devastating neurodegenerative disease associated with loss of dopaminergic neurons in the striatum, brain inflammation and accumulation of α-synuclein aggregates in the form of Lewy bodies [1]
The goal of this study was to test whether the peripheral injection of neural precursors (NPs) obtained from Embryonic stem cells (ESCs) and Mesenchymal stem cells (MSCs) could safely ameliorate the motor abnormalities and associated neuropathology in a mouse model of PD

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease. It is characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc) leading to aCells 2019, 8, 1359; doi:10.3390/cells8111359 www.mdpi.com/journal/cellsCells 2019, 8, 1359 progressive movement impairment that can include tremors, bradykinesia, rigidity, and postural instability [1,2]. Parkinson’s disease (PD) is the second most common neurodegenerative disease. It is characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc) leading to a. Cells 2019, 8, 1359 progressive movement impairment that can include tremors, bradykinesia, rigidity, and postural instability [1,2]. PD includes the aggregation of misfolded alpha-synuclein protein that generates intracellular Lewy bodies [2,6,7]. The presence of reactive microglia and an elevation in the number of astrocytes have been detected in the SNpc of PD patients and in mouse and primate models of PD systemically injected with There is an associated neuroinflammatory process governed by the action of microglia and astrocytes, which has been postulated to play a crucial role in PD pathogenesis [8,9].

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