Combined therapeutic strategy using erythropoietin and mesenchymal stem cells potentiates neurogenesis after transient focal cerebral ischemia in rats
Combined therapeutic strategy using erythropoietin and mesenchymal stem cells potentiates neurogenesis after transient focal cerebral ischemia in rats
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DOI：
10.1038/jcbfm.2008.40
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发表时间：
2008-09-01
影响因子：
6.3
通讯作者：
Bernaudin, Myriam
中科院分区：
文献类型：
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作者：
Esneault, Elise;Pacary, Emilie;Bernaudin, Myriam
许多研究表明，无论是促红细胞生成素（EPO）或间充质干细胞（MSC）治疗脑缺血的有益效果。除了神经保护作用外，不仅EPO而且MSC也有利于神经发生和功能恢复。为了进一步改善缺血后的组织修复，我们研究了在成年大鼠短暂局灶性脑缺血模型中，在EPO存在或不存在的情况下，全身给予MSC对神经发生和功能恢复的影响。缺血后24小时，将大鼠分为4组，即载体、MSC、EPO和MSC+EPO，并接受单次静脉注射MSC（2 × 10（6）细胞）和/或重复腹膜内给予EPO（1，000 UI/kg）3天。缺血后51天评估病变体积、MSC结果、神经发生和功能恢复。结果显示，MSC+EPO组侧脑室壁细胞增殖和神经发生沿着增加，而单独接受MSC或EPO的组中没有观察到显著影响。这种效应伴随着记忆性能的改善。在缺血半球检测到表达神经元或胶质细胞标记物的间充质干细胞。这些结果表明，EPO可能与MSC以协同方式发挥作用，以加强缺血后神经发生。
Many studies showed beneficial effects of either erythropoietin (EPO) or mesenchymal stem cells (MSCs) treatment in cerebral ischemia. In addition to a neuroprotective role, not only EPO but also MSC favors neurogenesis and functional recovery. In an attempt to further improve postischemic tissue repair, we investigated the effect of a systemic administration of MSC, in the presence or not of EPO, on neurogenesis and functional recovery in a transient focal cerebral ischemia model in the adult rat. Twenty-four hours after ischemia, the rats were divided into four groups, namely vehicle, MSC, EPO, and MSC+EPO, and received a single intravenous injection of MSC (2 x 10(6) cells) and/or a repeated intraperitoneal administration of EPO (1,000 UI/kg) for 3 days. The lesion volume, the MSC outcome, neurogenesis, and functional recovery were assessed 51 days after ischemia. The results showed that cellular proliferation and neurogenesis were increased along the lateral ventricle wall in the MSC+EPO group, whereas no significant effect was observed in groups receiving MSC or EPO alone. This effect was accompanied by an improvement of mnesic performances. Mesenchymal stem cells expressing neuronal or glial markers were detected in the ischemic hemisphere. These results suggest that EPO could act in a synergistic way with MSC to potentiate the postischemic neurogenesis.