Symbiosis Centre for Stem Cell Research, Symbiosis International (Deemed University), Pune 412115, India; Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Pune 412115, India.
Symbiosis Centre for Stem Cell Research, Symbiosis International (Deemed University), Pune 412115, India; Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Pune 412115, India.
Exp Neurol. 2022 Aug;354:114107. doi: 10.1016/j.expneurol.2022.114107. Epub 2022 May 10.
Neurodegenerative diseases (ND) are characterized by debilitating medical conditions that principally affect the neuronal cells in the human brain. One of the major reasons that there are no effective drugs for the treatment of ND is because researchers face technical challenges while conducting studies to understand the molecular mechanism behind ND. Although various studies have established in vitro neurodegenerative model systems, we feel that these model systems are not physiologically relevant, as they do not mimic the in vivo situation of chronic insult. Therefore, the primary aim of this study was to establish an in vitro neurodegenerative model system by inducing oxidative stress in such a way that the neuronal cells remain viable, but lose their structural and functional characteristics. Using a murine neuroblastoma cell line, Neuro-2a, we demonstrate that induction of oxidative stress significantly affects various neurite outgrowth parameters and reduces the expression of neuronal and autophagy markers without causing apoptosis in them. Previously, we have discussed the possible therapeutic applications of mesenchymal stromal cells (MSCs) and their secretome in the treatment of ND. Here, using two distinct approaches, we show that when Neuro-2a cells subjected to oxidative stress are exposed to MSC-derived conditioned medium (secretome), they exhibit a significant improvement in various neuronal parameters and in the expression of neuronal markers. Overall, our findings support the salutary role of MSC-derived secretome in rescuing the oxidative stress-induced loss of neurogenesis using a physiologically relevant in vitro model system. Our data underscore the propensity of the MSC-secretome in reversing ND.
神经退行性疾病（ND）的特征是使人衰弱的疾病，主要影响人类大脑中的神经元细胞。目前还没有有效的药物来治疗 ND，一个主要原因是研究人员在进行研究以了解 ND 背后的分子机制时面临技术挑战。尽管各种研究已经建立了体外神经退行性模型系统，但我们认为这些模型系统在生理学上并不相关，因为它们不能模拟体内慢性损伤的情况。因此，本研究的主要目的是通过诱导氧化应激来建立体外神经退行性模型系统，使神经元细胞保持存活，但失去其结构和功能特征。使用鼠神经母细胞瘤细胞系 Neuro-2a，我们证明诱导氧化应激显著影响各种神经突生长参数，并降低神经元和自噬标志物的表达，而不会导致它们凋亡。之前，我们已经讨论了间充质基质细胞（MSCs）及其分泌组在 ND 治疗中的可能治疗应用。在这里，我们使用两种不同的方法表明，当经历氧化应激的 Neuro-2a 细胞暴露于 MSC 衍生的条件培养基（分泌组）时，它们在各种神经元参数和神经元标志物的表达方面表现出显著改善。总的来说，我们的研究结果支持 MSC 衍生的分泌组在使用生理相关的体外模型系统拯救氧化应激诱导的神经发生损失方面的有益作用。我们的数据强调了 MSC 分泌组在逆转 ND 方面的倾向。
