Qilu Hospital, Wenhuaxi Road, Jinan, Shandong Province, 250014, China.
Department of Neurosurgery, Weifang Yidu Central Hospital, 4138 Linglongshan Road, Qingzhou, Shandong Province, 262500, China.
Cell Tissue Res. 2018 Apr;372(1):67-75. doi: 10.1007/s00441-017-2716-7. Epub 2017 Oct 30.
Intravenous administration of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been shown to promote nerve cell regeneration following traumatic brain injury (TBI). As the anti-oxidant defense systems in neuronal tissue including superoxide dismutase 2 (SOD2) are crucial to defend cell against oxidative stress. We proposed a new stratege to increase the therapeutic effect of MSCs by preventing cells death from oxidative stress. We overexpressed SOD2 in BM-MSCs, transplanted these MSCs into TBI model mice, assessed the protective effect of SOD2 against oxidation-induced apoptosis in BM-MSCs both in vitro and in vivo, evaluated brain functional recovery by the rotarod behavioral test, and tested the oxidation status of TBI mice brain after BM-MSCs transplantation by monitoring the superoxide dismutase, glutathione and malonaldehyde level. We found over-expression of SOD2 protected BM-MSCs from HO-induced cell apoptosis. Injection of SOD2 over-expressed BM-MSCs attenuated neuro-inflammation in the ipsilateral cortex of TBI mice, and protected TBI mice against loss of blood-brain barrier integrity. Furthermore, the rotarod behavioral test showed functional recovery of TBI mice after MSC treatment. Our experiments indicated that SOD2-over-expressed BM-MSCs have an improved therapeutic effect on brain injury treatment in TBI mice.
静脉注射骨髓间充质干细胞（BM-MSCs）已被证明可促进创伤性脑损伤（TBI）后的神经细胞再生。由于神经元组织中的抗氧化防御系统，包括超氧化物歧化酶 2（SOD2），对于抵抗氧化应激至关重要。我们提出了一种新策略，通过防止细胞因氧化应激而死亡来增加 MSC 的治疗效果。我们在 BM-MSCs 中转染 SOD2 过表达，将这些 MSC 移植到 TBI 模型小鼠中，评估 SOD2 在体外和体内对 BM-MSCs 氧化诱导凋亡的保护作用，通过转棒行为测试评估脑功能恢复情况，并通过监测超氧化物歧化酶、谷胱甘肽和丙二醛水平来测试 TBI 小鼠脑的氧化状态。我们发现 SOD2 的过表达可防止 HO 诱导的 BM-MSCs 细胞凋亡。SOD2 过表达的 BM-MSCs 注射可减轻 TBI 小鼠同侧皮质的神经炎症，并保护 TBI 小鼠免受血脑屏障完整性的丧失。此外，转棒行为测试表明 MSC 治疗后 TBI 小鼠的功能得到恢复。我们的实验表明，SOD2 过表达的 BM-MSCs 对 TBI 小鼠的脑损伤治疗具有更好的治疗效果。
