人脂肪来源干细胞衍生的外泌体对帕金森病转基因小鼠模型的治疗作用。
Therapeutic Effect of Human Adipocyte-derived Stem Cell-derived Exosomes on a Transgenic Mouse Model of Parkinson's Disease.
机构信息
Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, R.O.C.
Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
出版信息
In Vivo. 2023 Sep-Oct;37(5):2028-2038. doi: 10.21873/invivo.13300.
BACKGROUND/AIM: Stem cell therapy and regenerative medicine are promising for treating Parkinson's disease (PD) not only for the potential for cell replacement but also for the paracrine effect of stem cell secretion, especially proteins and nucleotide-enriched exosomes. This study investigated the neuroprotective effect of exosomes secreted from human adipocyte-derived stem cells (hADSCs) on PD.
MATERIALS AND METHODS
hADSCs were isolated from the visceral fat tissue of individuals without PD who underwent bariatric surgery and were validated using surface markers and differentiation ability. Exosomes were isolated from the culture medium of hADSCs through serial ultracentrifugation and validated. Condensed exosomes were administered intravenously to 12-week-old MitoPark mice, transgenic parkinsonism mouse model with conditional knockout of mitochondrial transcription factor A in dopaminergic neurons, monthly for 3 months. Motor function, gait, and memory were assessed monthly, and immunohistochemical analysis of neuronal and inflammatory markers was performed at the end of the experiments.
RESULTS
The hADSC-derived exosome-treated mice exhibited better motor function in beam walking and gait analyses than did the untreated mice. In the novel object recognition tests, the exosome-treated mice retained better memory function. Immunohistochemical analysis revealed that although exosome treatment did not prevent the loss of dopaminergic neurons in the substantia nigra of mice, it down-regulated microglial activation and neuroinflammation in the midbrain.
CONCLUSION
hADSC-derived exosomes were neuroprotective in this in vivo mouse model of PD, likely because of their anti-inflammatory effect. Use of hADSC-derived exosomes may offer several beneficial effects in stem cell therapy. Since they can also be produced at an industrial level, they are a promising treatment option for PD and other neurodegenerative diseases.
背景/目的：干细胞治疗和再生医学对于治疗帕金森病（PD）具有广阔的前景，不仅因为细胞替代的潜力，还因为干细胞分泌的旁分泌效应，特别是蛋白质和富含核苷酸的外泌体。本研究探讨了人脂肪干细胞（hADSCs）分泌的外泌体对 PD 的神经保护作用。
材料和方法
从接受减肥手术的无 PD 个体的内脏脂肪组织中分离 hADSCs，并通过表面标志物和分化能力进行验证。通过连续超速离心从 hADSCs 的培养基中分离外泌体并进行验证。将浓缩的外泌体每月一次静脉注射给 12 周龄的 MitoPark 小鼠，这是一种多巴胺能神经元中条件性敲除线粒体转录因子 A 的转基因帕金森病小鼠模型，共进行 3 个月。每月评估运动功能、步态和记忆，实验结束时进行神经元和炎症标志物的免疫组织化学分析。
结果
与未治疗的小鼠相比，hADSC 衍生的外泌体处理的小鼠在光束行走和步态分析中表现出更好的运动功能。在新物体识别测试中，外泌体处理的小鼠保留了更好的记忆功能。免疫组织化学分析显示，尽管外泌体治疗不能阻止小鼠黑质中多巴胺能神经元的丢失，但它下调了中脑的小胶质细胞激活和神经炎症。
结论
hADSC 衍生的外泌体在这种 PD 体内小鼠模型中具有神经保护作用，可能是因为其抗炎作用。使用 hADSC 衍生的外泌体可能在干细胞治疗中具有多种有益作用。由于它们也可以在工业水平上生产，因此它们是 PD 和其他神经退行性疾病的有前途的治疗选择。
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