Mesenchymal Stem Cells Overexpressing Interleukin-10 Promote Neuroprotection in Experimental Acute Ischemic Stroke.
Mesenchymal Stem Cells Overexpressing Interleukin-10 Promote Neuroprotection in Experimental Acute Ischemic Stroke.
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DOI：
10.1016/j.omtm.2017.06.005
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发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Okada T
中科院分区：
文献类型：
--
作者：
Nakajima M;Nito C;Sowa K;Suda S;Nishiyama Y;Nakamura-Takahashi A;Nitahara-Kasahara Y;Imagawa K;Hirato T;Ueda M;Kimura K;Okada T
白介素10是骨髓间充质干细胞移植对缺血性卒中后的神经保护作用的重要因素。我们的目的是利用大鼠短暂性大脑中动脉闭塞(MCAO)模型，通过将MSCs和体外IL-10基因转移与腺相关病毒(AAV)载体相结合来提高治疗效果。SD大鼠脑缺血90min后，分别于缺血再灌注后0或3h静脉注射MSCs或IL-10基因修饰的MSCs(MSC/IL-10)。在MCAO后7天内进行梗死灶、神经功能缺失和免疫学分析。单独移植0小时的MSCs和MSC/IL-10可显著缩小脑梗塞体积，改善运动功能。相反，在MCAO后72小时和7天，MSC/IL-10移植3小时，而不是单独移植MSCs，显著减少了脑梗塞体积(P<0.01)，改善了运动功能(P<0.01)。免疫学分析显示，与单独移植MSCs相比，MSC/IL-10移植显著抑制小胶质细胞的激活和促炎细胞因子的表达。此外，IL-10的过表达抑制了缺血侧移植的MSCs的神经元变性和提高了存活率。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，从而支持了急性缺血期神经元的存活。
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.
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影响因子：
11.2
作者：
Noro, T;Miyake, K;Shimada, T
通讯作者：
Shimada, T
DOI：
10.3988/jcn.2016.12.1.14
发表时间：
2016-01
期刊：
Journal of clinical neurology (Seoul, Korea)
影响因子：
--
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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