MicroRNA-21 Overexpression Promotes the Neuroprotective Efficacy of Mesenchymal Stem Cells for Treatment of Intracerebral Hemorrhage.

MicroRNA-21 Overexpression Promotes the Neuroprotective Efficacy of Mesenchymal Stem Cells for Treatment of Intracerebral Hemorrhage.
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MicroRNA-21 过表达促进间充质干细胞治疗脑出血的神经保护功效。

DOI:
10.3389/fneur.2018.00931
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发表时间:
2018
影响因子:
3.4
通讯作者:
He Z
He Z
中科院分区:
医学3区
文献类型:
--
作者:
Zhang H;Wang Y;Lv Q;Gao J;Hu L;He Z

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脑出血(ICH)发病率高,死亡率高,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),它已经在实验模型中显示出希望,并在治疗人类神经疾病方面具有巨大的潜力。然而,MSC治疗中的许多不足之处仍然需要解决,包括移植后存活率较低。此前,我们曾报道脑出血患者血液和脑组织中的microRNA-21(miR-21)表达下调。在这项研究中,我们旨在利用miR-21过表达的MSCs来检测其在脑出血中的作用和治疗效果。我们发现这种microRNA可以促进脑出血大鼠MSC的存活和神经功能的恢复。其作用机制涉及减少神经细胞的凋亡。此外,我们还证明了miR-21可以通过MSCs来源的外切体转运到神经元,并且它可以靶向瞬时受体电位Melastatin 7(TRPM7)来减轻脑出血后的神经元损伤。我们还观察到,在神经细胞中,NF-κB通路参与了miR-21的调节。综上所述,miR-21可显著提高脑出血后MSCs的存活率,并且过表达miR-21的MSCs明显改善了脑出血大鼠的神经功能。因此,移植高表达miR-21的MSCs可能为脑血管疾病的神经保护和治疗提供一种有效的策略。
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 (TRPM7) 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.
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