Third Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Neurosci Lett. 2013 Oct 25;554:70-5. doi: 10.1016/j.neulet.2013.08.047. Epub 2013 Sep 1.
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, β-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.
诱导多能干细胞（iPSCs）移植已显示出对缺血性中风有良好的治疗效果。然而，目前尚不清楚这种治疗方法是否会促进脑出血（ICH）后的恢复。在这项研究中，我们研究了 iPSCs 移植对大鼠实验性 ICH 的功能结果。iPSCs 是从一位 ICH 患者的成纤维细胞中衍生而来的，并被注射到大鼠 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，在移植后 4 周存活，并表现出神经细胞特异性标志物巢蛋白、β-微管蛋白和 GFAP。免疫组织化学染色显示，在 iPSCs 治疗大鼠的出血性脑组织周围，脑源性神经营养因子（BDNF）阳性细胞和血管内皮生长因子（VEGF）阳性细胞的密度显著增加。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 iPSCs 移植有助于改善实验性 ICH 大鼠的神经功能。其机制可能是由于神经元替代和神经营养因子的分泌增强。我们的数据表明，ICH 患者来源的 iPSCs 移植可能是一种治疗出血性中风的策略。
