Functional recovery after transplantation of induced pluripotent stem cells in a rat hemorrhagic stroke model
Functional recovery after transplantation of induced pluripotent stem cells in a rat hemorrhagic stroke model
复制标题
大鼠出血性中风模型中诱导多能干细胞移植后的功能恢复。
DOI：
10.1016/j.neulet.2013.08.047
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发表时间：
2013-10-25
影响因子：
2.5
通讯作者：
Xu, Yuming
中科院分区：
文献类型：
--
作者：
Qin, Jie;Gong, Guangming;Xu, Yuming
诱导多能干细胞（iPSC）移植已显示出对缺血性卒中的有希望的治疗效果。然而，目前尚不清楚这种治疗是否会促进脑出血（ICH）后的恢复。在这项研究中，我们研究了iPSCs移植在大鼠实验性ICH中的功能结果。IPSC来源于ICH患者的成纤维细胞，并注射到大鼠ICH的同侧。与载体和成纤维细胞注射相比，IPSCs移植显著改善了ICH后的神经功能。移植的iPSCs迁移到血肿周围的脑组织中，在移植4周后存活，并显示出神经细胞特异性生物标志物巢蛋白、β-微管蛋白和GFAP。免疫组织化学染色显示，iPSC处理组大鼠出血脑组织周围脑源性神经营养因子（BDNF）阳性细胞和血管内皮生长因子（VEGF）阳性细胞密度明显增加。此外，iPSCs治疗增加了血肿周围区域BDNF和VEGF的蛋白表达。这些发现表明，ICH患者来源的iPSC的移植有助于改善实验性ICH大鼠的神经功能。其机制可能与神经元替代和神经营养因子分泌增加有关。我们的数据表明，ICH患者来源的iPSC的移植可能是出血性卒中的治疗策略。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Transplantation of induced pluripotent stem cells (iPSCs) has shown promising therapeutic effects for ischemic stroke. However, it is not clear if this treatment would promote recovery after intracerebral hemorrhage (ICH). In this study, we investigated the functional outcome of iPSCs transplantation in experimental ICH in rats. IPSCs were derived from an ICH patient's fibroblasts and were injected into the ipsilateral side of ICH in rats. IPSCs transplantation significantly improved the neurological functions after ICH as compared to vehicle and fibroblast injection. The grafted iPSCs migrated into brain tissue around the hematoma, survived after 4 weeks of transplantation, and exhibited the neural cell-specific biomarkers nestin, beta-tubulin, and GFAP. Immunohistochemical staining showed that the densities of brain derived neurophic factors (BDNF)-positive cells and vascular endothelial growth factor (VEGF)positive cells were significantly increased around the hemorrhagic brain tissues of iPSCs-treated rats. In addition, iPSCs treatment increased the protein expression of BDNF and VEGF in the surrounding region of hematoma. These findings demonstrate that the transplantation of ICH patient-derived iPSCs contributes toward the improved neurological function in experimental ICH rats. The mechanisms are possibly due to neuronal replacement and enhanced secretion of neurophic factors. Our data suggest that transplantation of ICH patient-derived iPSCs may be a therapeutic strategy for hemorrhagic stroke. (C) 2013 Elsevier Ireland Ltd. All rights reserved.