Department of Ophthalmology, Bundang CHA Medical Center, CHA University, Seongnam, Gyeonggi-do, South Korea.
Department of Neurology, Bundang CHA Medical Center, CHA University, Seongnam, Gyeonggi-do, South Korea.
J Tissue Eng Regen Med. 2018 Mar;12(3):e1441-e1449. doi: 10.1002/term.2561. Epub 2017 Dec 5.
Different damage factors are known to trigger cell death in the optic nerves. Use of mesenchymal stem cells is a possible treatments option for traumatic optic nerve injury due to their ability to secrete protective cytokines and recovery factors. In this study, we investigated the neuroprotective effects of human placenta-derived mesenchymal stem cells (hPMSCs) using an established optic nerve compression model and model of R28 cells that were exposed to hypoxia. Forty percent of axon death was seen in induced in vivo optic nerve injury model (p < .05), and 70% of R28 cells exposed to cobalt chloride (CoCl ), leading to hypoxia, underwent apoptosis (p < .05). After intravenous injection of hPMSCs into tail vein, there was 25% improvement of axon survival in vivo (p < .05). R28 cells incubated with hPMSCs after exposure to hypoxic condition resulted in 50% increased cell survival compared with R28 cells without hPMSC exposure (p < .05), suggesting the active release of multiple factors related to cell survival. In addition, we found that Nf-κb protein mediates neuroprotection pathway via up-regulation of target proteins regulated by hPMSCs. Therefore, we assert that Nf-κb was one of the mediator proteins in a recovery pathway induced by hPMSCs. In conclusion, these indicate that transactivation of Nf-κb protein has a critical role in recovery mechanism by hPMSCs. We suggest that hPMSCs have abilities to recover neuronal damages by up-regulating the expression of genes associated with axon survival and can a better understanding of the possible role of hPMSCs in the treatment modalities of optic nerve injury.
已知不同的损伤因素可触发视神经细胞死亡。间充质干细胞由于能够分泌保护性细胞因子和恢复因子，因此是治疗创伤性视神经损伤的一种可能的治疗选择。在这项研究中，我们使用已建立的视神经压迫模型和暴露于缺氧的 R28 细胞模型，研究了人胎盘来源的间充质干细胞（hPMSC）的神经保护作用。在诱导的体内视神经损伤模型中，有 40%的轴突死亡（p<.05），而暴露于氯化钴（CoCl）导致缺氧的 70%的 R28 细胞发生凋亡（p<.05）。静脉注射 hPMSC 到尾静脉后，体内轴突存活有 25%的改善（p<.05）。在暴露于缺氧条件后与 hPMSC 孵育的 R28 细胞与未暴露于 hPMSC 的 R28 细胞相比，细胞存活率增加了 50%（p<.05），这表明 hPMSC 主动释放了与细胞存活相关的多种因子。此外，我们发现 Nf-κb 蛋白通过上调 hPMSC 调节的靶蛋白来介导神经保护途径。因此，我们断言 Nf-κb 是 hPMSC 诱导的恢复途径中的一种介导蛋白。总之，这些表明 Nf-κb 蛋白的转激活在 hPMSC 恢复机制中起着关键作用。我们建议 hPMSC 通过上调与轴突存活相关的基因的表达来恢复神经元损伤，这可以更好地理解 hPMSC 在视神经损伤治疗方式中的可能作用。
