Therapeutic Potential Of Menstrual Blood-Derived Endometrium Stem Cells On In Vitro And In Vivo Parkinson's Disease Models
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Date
2019-08
Authors
Li, Han
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Abstract
Human menstrual blood-derived endometrial stem cells (MenSCs) have shown therapeutic potential on various diseases by immunoregulation and tissue regeneration. However, their effects on Parkinson’s disease (PD) remain unknown. The aim of this study was to evaluate the protective function of MenSCs and their derivatives on in vitro and in vivo PD models. Neuroblastoma cell line (SH-SY5Y) and mouse midbrain slice were exposed to 1-methyl-4-phenylpyridinium (MPP+) to establish in vitro level PD models. Then, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to construct PD mouse model by intraperitoneal injection. After co-culture in vitro PD models with conditioned medium of MenSCs (MenSCs-CM), the viability of cell and midbrain slice were detected by Prestoblue and lactate dehydrogenase assay. The expression of inflammatory genes, anti-oxidant and apoptosis-related genes were detected by qRT-PCR. Dihydroethidium, Rhodamine123, and Annexin V/PI staining were used to detect reactive oxygen species (ROS), mitochondrial membrane potential, and cell apoptosis, respectively. Protein array was conducted to analyze factors inside MenSCs-CM. Moreover, MenSCs were transplanted to striatum (Str) region of PD mouse brain using a stereotaxic instrument. Survival time of MenSCs, dopamine (DA) level, expression of inflammatory genes and anti-oxidant genes were evaluated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to analyze pathways. Results showed MenSCs-CM attenuated MPP+-induced neurotoxicity by regulating pro- and anti-inflammatory cytokines expression, restoring mitochondrial membrane potential, reducing oxidative stress, and inhibiting cell apoptosis. The protective effect of MenSCs-CM on PD was also confirmed on slice level. Results showed MenSCs-CM significantly rescued midbrain slice viability reduction by anti-inflammatory and anti-oxidant properties (p<0.05 vs MPP+ + DMEM group). Protein array demonstrated there were at least 12 types of neurotrophic factors in MenSCs-CM, which may contribute to the protective function of MenSCs-CM in treating PD. In vivo experiments showed MenSCs survived in Str region of mouse brain for at least 28 days. Transplanted MenSCs significantly increased dopamine (DA) level in Str region and up-regulated the expression of anti-inflammatory genes (p<0.05 vs PD + PBS group). In addition, MenSCs increased the expression of anti-oxidant gene Nrf-2 and its down-stream genes (p<0.05 vs PD + PBS group). KEGG analysis showed factors secreted by MenSCs were involved in PI3K/Akt pathway, which may partly explain the anti-oxidant function of MenSCs. This study provided the first evidence that MenSCs-CM and MenSCs had protective effect on in vitro and in vivo PD models, suggesting MenSCs is a potential cell source used for cell-based or cell-free therapies in PD.
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Endometrium