Primer sequences for APP and β-actin.

Exosomes are extracellular vesicles, which are released into the extracellular space by all types of cells, especially stem cells. Compared with stem cells, exosomes are safer and can be considered one of the most promising therapeutic strategies for neurodegenerative disease. We examined the effect of exosomes derived from bone marrow mesenchymal stem cells (BM-MSC) on a rat model of Alzheimer’s disease (AD). For this purpose, male Wistar rats weighing 220–250 g were used. For the induction of AD, rats received a daily dosage of 100 mg/kg Aluminum chloride (Alcl3) by oral gavage for 60 days. Also, Primary BM-MSC was extracted from the femora of Wistar rats (male, 100–150 g). Extracted exosomes were Characterized and Qualified using TEM Microscope and Zetasizer Nano. Specific markers of exosomes were evaluated by Flow cytometry. MSC-extracted exosomes (150 µg/µl) were injected 2 or 5 times into the animals via tail vein on specific days. Our data revealed that receiving exosomes significantly prevented AlCl3-induced enhancement of hippocampal APP gene expression, beta-amyloid plaque formation, impairment of passive avoidance learning and spatial memory. However, exosome injections in healthy subjects caused some negative effects such as spatial memory impairment. It seems, MSC-derived exosomes can be considered as a candidate to prevent AD progression.外泌体（exosomes）是一类细胞外囊泡，由各类细胞分泌至细胞外间隙，尤以干细胞为主要分泌来源。相较于干细胞，外泌体安全性更高，可被视为神经退行性疾病最具潜力的治疗策略之一。本研究探讨了骨髓间充质干细胞（bone marrow mesenchymal stem cells, BM-MSC）来源外泌体对阿尔茨海默病（Alzheimer’s disease, AD）大鼠模型的干预效果。为此，本研究选用体重220~250 g的雄性Wistar大鼠作为实验对象。造模阶段，大鼠每日经口灌胃给予100 mg/kg氯化铝（aluminum chloride, AlCl₃），连续给药60天以诱导AD模型。此外，本研究从体重100~150 g的雄性Wistar大鼠股骨中提取原代骨髓间充质干细胞。提取得到的外泌体通过透射电子显微镜（TEM Microscope）与Zetasizer Nano粒度分析仪完成鉴定与质控，并采用流式细胞术（flow cytometry）检测外泌体的特异性标志物。将浓度为150 µg/µl的骨髓间充质干细胞来源外泌体，于特定天数通过尾静脉注射至大鼠体内，每组注射次数分为2次或5次。本研究结果显示，外泌体干预可显著抑制AlCl₃诱导的海马区淀粉样前体蛋白（amyloid precursor protein, APP）基因表达上调、β-淀粉样蛋白斑块沉积，以及被动回避学习与空间记忆功能损伤。但对健康大鼠进行外泌体注射则会引发部分不良反应，例如空间记忆功能受损。综上，骨髓间充质干细胞来源外泌体有望成为延缓阿尔茨海默病病情进展的潜在治疗候选方案。