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首页> 外文期刊>Molecular Therapy - Methods & Clinical Development >Mesenchymal Stem Cells Overexpressing Interleukin-10 Promote Neuroprotection in Experimental Acute Ischemic Stroke
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Mesenchymal Stem Cells Overexpressing Interleukin-10 Promote Neuroprotection in Experimental Acute Ischemic Stroke

机译：间充质干细胞过表达白细胞介素-10促进实验性急性缺血性卒中中的神经保护作用

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Interleukin (IL)-10 is a contributing factor to neuroprotection of mesenchymal stem cell (MSC) transplantation after ischemic stroke. Our aim was to increase therapeutic effects by combining {MSCs} and ex?vivo IL-10 gene transfer with an adeno-associated virus (AAV) vector using a rat transient middle cerebral artery occlusion (MCAO) model. Sprague-Dawley rats underwent 90?min {MCAO} followed by intravenous administration of {MSCs} alone or IL-10 gene-transferred {MSCs} (MSC/IL-10) at 0 or 3?hr after ischemia reperfusion. Infarct lesions, neurological deficits, and immunological analyses were performed within 7?days after MCAO. 0-hr transplantation of {MSCs} alone and MSC/IL-10 significantly reduced infarct volumes and improved motor function. Conversely, 3-hr transplantation of MSC/IL-10, but not {MSCs} alone, significantly reduced infarct volumes (p? 0.01) and improved motor function (p? 0.01) compared with vehicle groups at 72?hr and 7?days after MCAO. Immunological analysis showed that MSC/IL-10 transplantation significantly inhibits microglial activation and pro-inflammatory cytokine expression compared with {MSCs} alone. Moreover, overexpressing IL-10 suppressed neuronal degeneration and improved survival of engrafted {MSCs} in the ischemic hemisphere. These results suggest that overexpressing IL-10 enhances the neuroprotective effects of {MSC} transplantation by anti-inflammatory modulation and thereby supports neuronal survival during the acute ischemic phase.
机译：白细胞介素（IL）-10是缺血性卒中后间充质干细胞（MSC）移植的神经保护剂的贡献因素。我们的目的是通过使用大鼠瞬时中间脑动脉闭塞（MCAO）模型将{MSCS}和EXα和EXα和EL-10基因转移与腺相关病毒（AAV）载体组合来提高治疗效果。 Sprague-Dawley大鼠在缺血再灌注后，在术后90？min {MCAO}接下来静脉介导或单独施用{MSCS}或在0或3的IL-10基因转移的{MSCS}（MSC / IL-10）。梗塞病变，神经缺陷和免疫学分析在MCAO后的7天内进行。单独的{MSCS}的0-HR移植和MSC / IL-10显着降低了梗塞体积和改进的电机功能。相反，单独的MSC / IL-10的3-HR移植，但不是{MSCs}，与72Ω·HR和7的载体组相比，梗塞功能（P？<0.01）和改善的电动机功能（P？<0.01） ？MCAO后的天。免疫分析表明，与{MSCs}相比，MSC / IL-10移植显着抑制了微胶质激活和促炎细胞因子表达。此外，过表达IL-10抑制了缺血半球中的神经元变性并改善了植入的{MSCs}的生存。这些结果表明，过表达IL-10通过抗炎调节增强了{MSC}移植的神经保护作用，从而支持急性缺血期期间的神经元生存率。

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