Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.
Department of Computer Sciences, University of Verona, 37134 Verona, Italy.
Int J Mol Sci. 2020 May 21;21(10):3651. doi: 10.3390/ijms21103651.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motoneurons. To date, there is no effective treatment available. Exosomes are extracellular vesicles that play important roles in intercellular communication, recapitulating the effect of origin cells. In this study, we tested the potential neuroprotective effect of exosomes isolated from adipose-derived stem cells (ASC-exosomes) on the in vivo model most widely used to study ALS, the human SOD1 gene with a G93A mutation (SOD1(G93A)) mouse. Moreover, we compared the effect of two different routes of exosomes administration, intravenous and intranasal. The effect of exosomes administration on disease progression was monitored by motor tests and analysis of lumbar motoneurons and glial cells, neuromuscular junction, and muscle. Our results demonstrated that repeated administration of ASC-exosomes improved the motor performance; protected lumbar motoneurons, the neuromuscular junction, and muscle; and decreased the glial cells activation in treated SOD1(G93A) mice. Moreover, exosomes have the ability to home to lesioned ALS regions of the animal brain. These data contribute by providing additional knowledge for the promising use of ASC-exosomes as a therapy in human ALS.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是运动神经元进行性退化。迄今为止，尚无有效的治疗方法。外泌体是细胞外囊泡，在细胞间通讯中发挥重要作用，可再现起源细胞的作用。在这项研究中，我们测试了从脂肪干细胞（ASC-exosomes）分离的外泌体对最广泛用于研究 ALS 的体内模型的潜在神经保护作用，即具有 G93A 突变的人 SOD1 基因（SOD1（G93A））小鼠。此外，我们比较了两种不同外泌体给药途径（静脉内和鼻内）的效果。通过运动测试以及对腰椎运动神经元和神经胶质细胞、神经肌肉接头和肌肉的分析来监测外泌体给药对疾病进展的影响。我们的结果表明，重复给予 ASC-exosomes 可改善运动表现；保护腰椎运动神经元、神经肌肉接头和肌肉；并减少治疗性 SOD1（G93A）小鼠中神经胶质细胞的激活。此外，外泌体具有向病变的 ALS 动物大脑区域归巢的能力。这些数据通过提供有关 ASC-exosomes 作为人类 ALS 治疗方法的有前途的应用的更多知识做出了贡献。
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