The transplantation of mesenchymal stem cells (MSCs) is of main approaches in regenerative therapy for stroke. Due to the potential tumorigenicity and low survival rate of transplanted cells, focuses have been shifted from cell replacement to their paracrine effects. Therefore, stem cell‐conditioned medium (CM) therapy has emerged as an alternative candidate. Here, we investigated the effect of CM derived from human embryonic MSCs on experimental ischemic stroke. Wistar rats underwent ischemic stroke by the right middle cerebral artery occlusion (MCAO). CM was infused either one time (1 hr post‐MCAO) or three times (1, 24, and 48 hr post‐MCAO) through guide cannula into the left lateral ventricle. Neurological functions were evaluated using Bederson's test and modified Neurological Severity Score on Days 1, 3, and 7 following MCAO. Infarction volumes and cerebral edema were measured on Days 3 and 7. growth‐associated protein‐43, synaptophysin, cAMP response element‐binding protein, and phosphorylated‐cAMP response element‐binding protein levels were also assessed in peri‐ischemic cortical tissue on Day 7 postsurgery. Our results indicated that three times injections of CM could significantly reduce body weight loss, mortality rate, infarct volumes, cerebral edema, and improve neurological deficits in MCAO rats. Moreover, three injections of CM could restore decreased levels of synaptic markers in MCAO rats up to its normal levels observed in the sham group. Our data suggest that using the CM obtained from embryonic stem cells–MSCs could be a potent therapeutic approach to attenuate cerebral ischemia insults which may be partly mediated through modulation of synaptic plasticity.

中文翻译：

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人胚胎干细胞衍生的间充质干细胞的条件培养基可减轻神经功能障碍并改善实验性中风的突触恢复。

间充质干细胞（MSCs）的移植是中风再生治疗的主要方法。由于移植细胞的潜在致瘤性和低存活率，重点已从细胞替代转移到旁分泌作用。因此，干细胞条件培养基 (CM) 疗法已成为替代候选者。在这里，我们研究了源自人胚胎 MSC 的 CM 对实验性缺血性中风的影响。Wistar 大鼠因右侧大脑中动脉闭塞 (MCAO) 而遭受缺血性中风。通过引导套管将 CM 输注一次（MCAO 后 1 小时）或 3 次（MCAO 后 1、24 和 48 小时）进入左侧心室。在 MCAO 后的第 1、3 和 7 天，使用 Bederson 测试和修正的神经严重程度评分评估神经功能。在第 3 天和第 7 天测量梗塞体积和脑水肿。在第 1 天还评估了缺血周围皮层组织中的生长相关蛋白 43、突触素、cAMP 反应元件结合蛋白和磷酸化 cAMP 反应元件结合蛋白水平7 术后。我们的结果表明，CM 3 次注射可显着降低 MCAO 大鼠的体重减轻、死亡率、梗死体积、脑水肿，并改善神经功能缺损。此外，CM 的 3 次注射可以将 MCAO 大鼠中降低的突触标志物水平恢复到假手术组中观察到的正常水平。