Conditioned Medium of Human Menstrual Blood-Derived Endometrial Stem Cells Protects Against MPP+-Induced Cytotoxicity in vitro

Conditioned Medium of Human Menstrual Blood-Derived Endometrial Stem Cells Protects Against MPP+-Induced Cytotoxicity in vitro
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人经血来源的子宫内膜干细胞的条件培养基在体外可防止 MPP 诱导的细胞毒性

DOI:
10.3389/fnmol.2019.00080
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发表时间:
2019-04-05
影响因子:
4.8
通讯作者:
Lin, Juntang
Lin, Juntang
中科院分区:
医学2区
文献类型:
--
作者:
Li, Han;Yahaya, Badrul Hisham;Lin, Juntang

文献摘要

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间充质干细胞(MSCs)显示出治疗帕金森病(PD)的潜力。然而,人经血来源的子宫内膜干细胞(MenSCs-CM)的条件培养基是否具有缓解PD综合征的功能尚不清楚。本研究以神经毒物1-甲基-4-苯基吡啶(MPP+)诱导人神经母细胞瘤细胞SH-SY 5 Y产生一系列PD反应特征。将该细胞模型与24 h/48 h收集的MenSCs-CM培养不同天数后,检测细胞活力、促炎细胞因子、线粒体膜电位(Delta psi m)、氧化应激和细胞凋亡。最后,采用蛋白质分析法检测MenSCs-CM中12种神经营养因子的表达。结果显示MPP+可引起SH-SY 5 Y细胞活力下降,并呈剂量和时间依赖性。MPP(+)处理导致炎症,线粒体功能障碍,活性氧(ROS)的产生积累,并在其1050浓度的SH-SY 5 Y的凋亡。48小时收集的MenSCs-CM和与MPP+处理的SH-SY 5 Y一起培养2天是增加细胞活力的优化条件。此外,MenSCs-CM可有效对抗MPP+诱导的炎症、Δ psi m损失、ROS产生,并可显著减少凋亡晚期的细胞数量。蛋白质检测显示,MenSCs-CM含有多种神经保护因子。我们的研究首次提供了MenSCs-CM在多个方面对MPP+诱导的细胞毒性具有保护作用的证据,并首次表明MenSC可以向培养基中释放至少12种神经营养因子,这可能有助于MenSCs-CM治疗PD的保护功能。该研究启示MenSCs-CM在PD的治疗中是有益的,并且可能也用于其他神经退行性疾病。
Mesenchymal stem cells (MSCs) showed the potential to treat Parkinson's disease (PD). However, it is unknown whether the conditioned medium of human menstrual blood-derived endometrial stem cells (MenSCs-CM) has the function to alleviate syndromes of PD. In this study, human neuroblastoma SH -SY5Y cells were exposed to neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) for inducing a range of response characteristics of PD. After culturing this cell model with 24 h/48 h collected MenSCs-CM for different days, cell viability, pro-inflammation cytokines, mitochondrial membrane potential (Delta psi m), oxidative stress, and cell apoptosis were detected. Finally, protein assay was performed to detect 12 kinds of neurotrophic factors inside MenSCs-CM. Our results showed that MPP+ caused SH-SY5Y cell viability reduction as an increasing dose and time dependent manner. MPP(+)treatment resulted in inflammation, mitochondrial dysfunction, reactive oxygen species (ROS) production accumulation, and apoptosis of SH-SY5Y at its 1050 concentration. Forty-eight hours-collected MenSCs-CM and culturing with the MPP+-treated SH-SY5Y for 2 days are the optimized condition to increase cell viability. Besides, MenSCs-CM was efficacious against MPP+ induced inflammation, Delta psi m loss, ROS generation, and it could significantly decrease cells numbers in late apoptosis stage. What's more, protein assay showed that MenSCs-CM contained various neuroprotective factors. Our study provided the first evidence that MenSCs-CM has a protective effect on MPP+-induced cytotoxicity in various aspects, and firstly showed that MenSCs can release at least 12 kinds of neurotrophic factors to medium, which may contribute to the protective function of MenSCs-CM to treat PD. This research enlightening that MenSCs-CM is beneficial in the therapy for PD and probably also for other neurodegenerative diseases.