Zhang Heyu, Wang Yanzhe, Lv Qing, Gao Jun, Hu Liuting, He Zhiyi
Department of Neurology, The First Affiliated Hospital of China Medical University, Liaoning, China.
Front Neurol. 2018 Nov 6;9:931. doi: 10.3389/fneur.2018.00931. eCollection 2018.
Intracerebral hemorrhage (ICH) has high morbidity and mortality, with no effective treatment at present. One possible therapeutic strategy involves the use of mesenchymal stem cells (MSCs), which have shown promise in experimental models and have great potential for treating nervous illnesses in humans. However, many deficiencies in MSC treatment still need to be addressed, including their poor survival rate post-transplantation. Previously, we reported that the microRNA-21 (miR-21) is downregulated in ICH patients' blood and brain tissue. In this study, we aimed to examine its role and therapeutic efficacy in ICH using miR-21-overexpressing MSCs. We found that this microRNA can enhance MSC survival and recovery of neurological function in ICH rats. Its mechanism of action involves reduced neuronal apoptosis. In addition, we demonstrated that miR-21 can be transported to neurons through exosomes derived from MSCs and that it can target transient receptor potential melastatin 7 ( to alleviate neuronal injury following ICH. We also observed that the NF-κB pathway is involved in the regulation of miR-21 in neural cells. In conclusion, miR-21 significantly enhances the survival of MSCs in ICH, and miR-21-overexpressing MSCs clearly improved neurological function in ICH rats. Transplantation of miR-21-overexpressing MSCs may, therefore, provide an effective strategy for neuroprotection and treatment of cerebrovascular diseases.
脑出血（ICH）具有高发病率和死亡率，目前尚无有效的治疗方法。一种可能的治疗策略涉及使用间充质干细胞（MSCs），其在实验模型中已显示出前景，并且在治疗人类神经疾病方面具有巨大潜力。然而，MSCs治疗仍存在许多不足之处需要解决，包括移植后的存活率低。此前，我们报道过微小RNA-21（miR-21）在ICH患者的血液和脑组织中表达下调。在本研究中，我们旨在使用过表达miR-21的MSCs来研究其在ICH中的作用和治疗效果。我们发现这种微小RNA可以提高ICH大鼠中MSCs的存活率并促进神经功能恢复。其作用机制涉及减少神经元凋亡。此外，我们证明miR-21可以通过MSCs衍生的外泌体转运至神经元，并且它可以靶向瞬时受体电位香草酸亚型7（TRPM7）以减轻ICH后的神经元损伤。我们还观察到NF-κB通路参与神经细胞中miR-2l的调节。总之，miR-21显著提高了ICH中MSCs的存活率，过表达miR-21的MSCs明显改善了ICH大鼠的神经功能。因此，移植过表达miR-21的MSCs可能为神经保护和治疗脑血管疾病提供一种有效的策略。
