Functional recovery of the murine brain ischemia model using human induced pluripotent stem cell-derived telencephalic progenitors
Functional recovery of the murine brain ischemia model using human induced pluripotent stem cell-derived telencephalic progenitors
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DOI：
10.1016/j.brainres.2012.03.049
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发表时间：
2012-06-12
期刊：
影响因子：
2.9
通讯作者：
Takahashi, Jun
中科院分区：
文献类型：
--
作者：
Gomi, Masanori;Takagi, Yasushi;Takahashi, Jun
诱导多能干细胞(IPS)具有与胚胎干细胞相似的自我更新和多潜能特性。它们是细胞替代疗法合适的细胞来源的一个很好的候选者。在这项研究中，我们将人iPS细胞衍生的神经前体细胞移植到缺血小鼠的大脑中。采用类胚体集合体(SFEB)无血清培养方法，将人iPS细胞分化为神经前体细胞。采用线栓法制备局灶性脑缺血模型。缺血诱导后1周将供体细胞移植到缺血侧纹状体内。细胞在移植部位存活，部分细胞沿外囊和胼胝体迁移。端脑基本标志Nkx2.1阳性的细胞迁移到端脑的基底部。在迁移到端脑顶叶部分的细胞中检测到了顶叶端脑标记Emx1。SFEB分化为各种类型的神经元，逆行示踪研究表明，分化后的细胞整合到宿主神经回路中。移植组大鼠的行为恢复明显增强。我们的结果表明，人iPS细胞来源的神经前体细胞在缺血脑内存活和迁移，并通过神经回路重建促进功能恢复。(C)2012爱思唯尔B.V.保留所有权利。
Induced pluripotent stem (iPS) cells possess the properties of self-renewal and pluripotency, similar to embryonic stem cells. They are a good candidate as a source of suitable cells for cell replacement therapy. In this study, we transplanted human iPS cell-derived neural progenitors into an ischemic mouse brain. Human iPS cells were differentiated into neuronal progenitors by serum-free culture of embryoid body-like aggregates (SFEBs). Focal cerebral ischemia was induced by occluding the middle cerebral artery using the intraluminal filament technique. Donor cells were transplanted into the ischemic lateral striatum 1 week after ischemia induction. Cells survived at the transplantation site, with migration of a proportion of cells along the external capsule and corpus callosum. Cells that were positive for the basal telencephalon marker, Nkx2.1, migrated into the basal part of the telencephalon. The pallial telencephalon marker, Emx1, was detected in cells that had migrated into the pallial part of the telencephalon. SFEBs differentiated into various types of neurons, and a retrograde tracer labeling study showed that differentiated cells integrated into host neural circuitry. Behavioral recovery was significantly enhanced in the transplanted group. Our results suggest that human iPS cell-derived neuronal progenitors survive and migrate in the ischemic brain, and contribute toward functional recovery via neural circuit reconstitution. (C) 2012 Elsevier B.V. All rights reserved.