Sadeghi Atefeh, Noorbakhshnia Maryam, Khodashenas Shabanali
Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Thalassemia Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
PLoS One. 2025 May 6;20(5):e0320883. doi: 10.1371/journal.pone.0320883. eCollection 2025.
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.
外泌体是细胞外囊泡,由所有类型的细胞,尤其是干细胞释放到细胞外空间。与干细胞相比,外泌体更安全,可被视为神经退行性疾病最有前景的治疗策略之一。我们研究了骨髓间充质干细胞(BM-MSC)来源的外泌体对阿尔茨海默病(AD)大鼠模型的影响。为此,使用了体重220-250克的雄性Wistar大鼠。为诱导AD,大鼠每天经口灌胃给予100毫克/千克氯化铝(Alcl3),持续60天。此外,从Wistar大鼠(雄性,100-150克)的股骨中提取原代BM-MSC。使用透射电子显微镜和纳米Zetasizer对提取的外泌体进行表征和鉴定。通过流式细胞术评估外泌体的特异性标志物。在特定日期通过尾静脉将MSC提取的外泌体(150微克/微升)注射到动物体内2次或5次。我们的数据显示,接受外泌体可显著预防AlCl3诱导的海马APP基因表达增强、β-淀粉样蛋白斑块形成、被动回避学习和空间记忆受损。然而,向健康受试者注射外泌体导致了一些负面影响,如空间记忆受损。看来,MSC来源的外泌体可被视为预防AD进展的候选物。