干细胞治疗和再生医学在治疗帕金森病（PD）方面具有潜力，不仅由于细胞替代的潜力，还由于干细胞分泌的旁分泌作用，尤其是蛋白质和富含核苷酸的外泌体。本研究调查了从人脂肪细胞源干细胞（hADSCs）分泌的外泌体对PD的神经保护作用。从未患PD的肥胖手术患者的内脏脂肪组织中分离出hADSCs，并通过表面标记物和分化能力进行验证。通过连续超速离心从hADSCs的培养基中分离和验证外泌体。经过浓缩的外泌体每月静脉注射到12周龄的MitoPark小鼠体内，这是一种转基因帕金森症小鼠模型，其中多巴胺能神经元中条件敲除线粒体转录因子A。每月评估运动功能、步态和记忆，并在实验结束时进行神经元和炎症标记物的免疫组化分析。通过梁行走和步态分析，hADSC源外泌体处理的小鼠的运动功能表现较未处理小鼠更好。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防止小鼠黑质致密部位多巴胺能神经元的丧失，但它调节了脑中段的小胶质细胞激活和神经炎症。hADSC源外泌体在这个PD体内小鼠模型中具有神经保护作用，可能归因于其抗炎作用。使用hADSC源外泌体可能在干细胞治疗中提供几种有益效果。由于它们还可以工业化生产，它们是PD和其他神经退行性疾病的一种有希望的治疗选择。版权所有2023年，国际抗癌研究学院（Dr. George J. Delinasios）。保留所有权利。

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.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.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.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.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.