An in vitro mouse model for retinal ganglion cell replacement therapy using eye-like structures differentiated from ES cells
An in vitro mouse model for retinal ganglion cell replacement therapy using eye-like structures differentiated from ES cells
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DOI：
10.1016/j.exer.2007.01.007
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发表时间：
2007-05-01
影响因子：
3.4
通讯作者：
Kunisada, Takahiro
中科院分区：
文献类型：
--
作者：
Aoki, Hitomi;Hara, Akira;Kunisada, Takahiro
本研究的目的是调查胚胎干 (ES) 细胞衍生的眼样结构的发育潜力，作为 N-甲基-D-天冬氨酸 (NMDA) 诱导损伤的视网膜替代细胞治疗模型。为此，小鼠 ES 细胞在体外诱导分化为眼样结构 10 天，并与经过或未经 NMDA 处理的成年小鼠视网膜共培养。 NMDA 诱导内神经视网膜中的兴奋毒性神经元细胞死亡，特别是在神经节细胞层内。共培养10天后，固定标本，包埋于石蜡中并进行免疫组织化学分析。当与成年小鼠视网膜共培养时，移植的眼状结构分化为 Tujl 阳性神经元，然后细胞迁移到神经节细胞层。当与 NMDA 处理的视网膜共培养时，大多数迁移到神经节细胞层的细胞表达神经节细胞特异性标记 Hu 和 Bm3b。小鼠ES细胞衍生的眼样结构含有可以在体外分化为宿主神经节细胞层中的神经节样细胞的细胞群。此外，当 NMDA 诱导神经节细胞特异性损伤时，它们对神经节细胞层的贡献更为突出。这些发现表明，由 ES 细胞生成的眼状结构制备的细胞可能可用于细胞替代疗法，也可以作为此类疗法的模型系统。 (C) 2007 Elsevier Ltd. 保留所有权利。
The aim of this study was to investigate the developmental potential of embryonic stem (ES) cell-derived eye-like structures as a replacement cell therapy model for retinas with N-methyl-D-aspartate (NMDA)-induced damage. For this purpose mouse ES cells were induced to differentiate into eye-like structures in vitro for 10 days and co-cultured with adult mouse retina treated with or without NMDA treatment. NMDA induces excitotoxic neuronal cell death in the inner neural retina, specifically within the ganglion cell layer. After 10 days of co-culture, the specimens were fixed, embedded in paraffin wax and analyzed by immunohistochemistry. Transplanted eye-like structures differentiate into Tujl-positive neurons when co-cultured with an adult mouse retina and the cells then migrate into the ganglion cell layer. When co-cultured with an NMDA-treated retina, most of the cells migrating into the ganglion cell layer express the ganglion cell-specific markers Hu and Bm3b. Murine ES cell-derived eye-like structures contain cell populations that can differentiate into ganglion-like cells in the host ganglion cell layer in vitro. Moreover, their contribution to the ganglion cell layer was more prominent when ganglion cell specific damage was induced by NMDA administration. These findings suggest that cells prepared from the eye-like structures generated from ES cells may be useful for cell replacement therapy and may also serve as a model system for such therapies. (C) 2007 Elsevier Ltd. All rights reserved.