Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Int J Mol Sci. 2022 Apr 29;23(9):4967. doi: 10.3390/ijms23094967.
Neuroinflammation is involved in neuronal cell death that occurs in neurodegenerative diseases such as Alzheimer's disease (AD). Microglia play important roles in regulating the brain amyloid beta (Aβ) levels, so immunomodulatory properties exerted by mesenchymal stem cells may be exploited to treat this pathology. The evidence suggests that the mechanism of action of human amniotic fluid stem cells (hAFSCs) is through their secretome, which includes exosomes (exo).
We examined the effect of exosomes derived from human amniotic fluid stem cells (hAFSCs-exo) on activated BV-2 microglia cells by lipopolysaccharide (LPS) as a neuroinflammation model. To investigate the exo effect on the interplay between AD neurons and microglia, SH-SY5Y neuroblastoma cells treated with Aβ were exposed to a conditioned medium (CM) obtained from activated BV-2 or co-culture systems.
We found that the upregulation of the markers of pro-inflammatory microglia was prevented when exposed to hAFSC-exo whereas the markers of the anti-inflammatory macrophage phenotype were not affected. Interestingly, the hAFSC-exo pretreatment significantly inhibited the oxidative stress rise and apoptosis occurring in the neurons in presence of both microglia and Aβ.
We demonstrated that hAFSC-exo mitigated an inflammatory injury caused by microglia and significantly recovered the neurotoxicity, suggesting that hAFSC-exo may be a potential therapeutic agent for inflammation-related neurological conditions, including AD.
神经炎症参与了神经退行性疾病（如阿尔茨海默病）中神经元细胞的死亡。小胶质细胞在调节大脑淀粉样蛋白 β（Aβ）水平方面发挥着重要作用，因此间充质干细胞的免疫调节特性可能被用于治疗这种病理。有证据表明，人羊水干细胞（hAFSCs）的作用机制是通过其外泌体（exo）的分泌组。
我们通过脂多糖（LPS）作为神经炎症模型，研究了人羊水干细胞来源的外泌体（hAFSCs-exo）对激活的 BV-2 小胶质细胞的影响。为了研究外泌体对 AD 神经元和小胶质细胞相互作用的影响，用 Aβ 处理 SH-SY5Y 神经母细胞瘤细胞，并使其暴露于由激活的 BV-2 或共培养系统获得的条件培养基（CM）中。
我们发现，当暴露于 hAFSC-exo 时，促炎小胶质细胞标志物的上调被阻止，而抗炎巨噬细胞表型的标志物不受影响。有趣的是，hAFSC-exo 预处理显著抑制了在存在小胶质细胞和 Aβ 的情况下神经元中发生的氧化应激升高和细胞凋亡。
我们证明 hAFSC-exo 减轻了小胶质细胞引起的炎症损伤，并显著恢复了神经毒性，这表明 hAFSC-exo 可能是一种治疗与炎症相关的神经疾病的潜在治疗剂，包括 AD。
