Transplantation of human neuro-epithelial-like stem cells derived from induced pluripotent stem cells improves neurological function in rats with experimental intracerebral hemorrhage
Transplantation of human neuro-epithelial-like stem cells derived from induced pluripotent stem cells improves neurological function in rats with experimental intracerebral hemorrhage
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DOI：
10.1016/j.neulet.2013.05.007
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发表时间：
2013-08-26
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;Song, Bo;Xu, Yuming
脑出血（ICH）的致残率和病死率较高，目前尚无特异性靶向治疗。从ICH患者的体细胞产生的诱导多能干细胞（iPSC）具有个体化脑保护的治疗潜力。然而，ICH患者来源的iPSCs是否可以分化为神经上皮样干细胞（内斯）细胞以及这些内斯细胞是否可以促进脑损伤后的功能恢复尚不清楚。在这里，我们表明，来自ICH患者的成纤维细胞可以通过携带定义的转录因子（OCT 4，SOX 2，KLF 4和c-MYC）的慢病毒载体有效地重编程为iPSC。这些iPSC具有典型的形态、表面抗原、自我更新能力和分化成与人胚胎干细胞（hESC）相似的所有三个胚胎胚层的细胞类型的能力。采用无血清神经分化培养基诱导iPSCs向内斯细胞分化。随后，将来自ICH患者来源的iPSC的内斯细胞移植到实验性ICH损伤的大鼠的血肿周围。有趣的是，NES细胞移植后，实验性ICH大鼠的神经功能障碍得到恢复。移植的内斯细胞迁移至血肿周围，存活并分化为神经元样细胞。我们的研究表明，人iPS源性内斯细胞移植是治疗脑出血损伤的有效方法，神经功能的改善部分是由于神经元的替代和再生。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Specific targeted therapy for intracerebral hemorrhage (ICH), which has high disability and case-fatality rate, is currently not available. Induced pluripotent stem cells (iPSCs) generated from somatic cells of ICH patients have therapeutic potential for individualized cerebral protection. While, whether ICH patient-originated iPSCs could differentiate into neuro-epithelial-like stem (NES) cells and whether such NES cells could improve functional recovery in the hemorrhage-injured brain are unclear. Here, we showed that fibroblasts from an ICH patient can be efficiently reprogrammed to iPSCs by lentiviral vectors carrying defined transcription factors (OCT4, SOX2, KLF4, and c-MYC). These iPSCs have the typical morphology, surface antigens, capability of self-renewal and differentiating into cell types of all three embryonic germ layers that are similar to human embryonic stem cells (hESCs). Using defined serum-free neural differentiation medium, we induced the iPSCs differentiate into NES cells. Subsequently, the NES cells from ICH patient-originated iPSCs were transplanted into the perihematoma of rats with experimental ICH injury. Intriguingly, recovery of neurological dysfunction in experimental ICH rats was observed post-NES cells graftage. Transplanted NES cells migrated to the surrounding area of hematoma, survived and differentiated into neuron-like cells. Our study demonstrates that the transplantation of human iPS-originated NES cells is an effective approach of treating ICH injury and the improvement of neural function is partially due to neuronal replacement and regeneration. (C) 2013 Elsevier Ireland Ltd. All rights reserved.