Transplantation of EGF-responsive neurospheres from GFP transgenic mice into the eyes of rd mice

Transplantation of EGF-responsive neurospheres from GFP transgenic mice into the eyes of rd mice
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DOI:
10.1016/s0006-8993(02)02906-2
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发表时间:
2002-07-12
期刊:
影响因子:
2.9
通讯作者:
Young, MJ
Young, MJ
中科院分区:
医学3区
文献类型:
--
作者:
Lu, B;Kwan, T;Young, MJ

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从中枢神经系统不同区域分离干细胞增加了将它们用作细胞移植的供体细胞来源的可能性,它们为修复患病的大脑、脊髓和视网膜提供了巨大的希望。在这里,我们研究了从绿色荧光蛋白转基因小鼠脑中分离的EGF反应神经球的迁移、整合和分化,并将其移植到视网膜色素变性模型成年RD小鼠的眼睛中。虽然新鲜分离的出生后第8天的视网膜移植表达了许多成熟视网膜的标志物(如视紫红质、蛋白激酶C),但很少有移植细胞迁移到宿主视网膜。相反,EGF反应神经球很容易迁移到剩余的宿主视网膜并与之整合,但分化为成熟视网膜神经元的能力非常有限。虽然这里使用的祖细胞表现出与宿主视网膜整合并发展出视网膜细胞的某些属性的非凡能力,但未能完全分化为视网膜细胞表明,它们已经表达了一定程度的终末承诺,排除了使用它们来取代丢失的光感受器的可能性。(C)2002 Elsevier Science B.V.保留所有权利。
The isolation of stem cells from various regions of the central nervous system has raised the possibility of using them as a donor cell source for cell transplantation, where they offer great promise for repair of the diseased brain, spinal cord, and retina. Here, we have studied the migration, integration, and differentiation of EGF-responsive neurospheres isolated from the brains of green fluorescent protein transgenic mice and transplanted into the eyes of mature rd mice, a model of retinitis pigmentosa. While grafts of freshly isolated postnatal day 8 retina expressed many markers characteristic of mature retina (e.g. rhodopsin, protein kinase C), very few of the grafted cells migrated into host retina. EGF-responsive neurospheres, conversely, readily migrated into and integrated with the remaining host retina, but showed a very limited ability to differentiate into mature retinal neurons. While the progenitor cells used here show remarkable ability to integrate with host retina and develop some attributes of retinal cells, the failure to fully differentiate into retinal cells suggests that they already express some level of terminal commitment that precludes using them to replace lost photoreceptors. (C) 2002 Elsevier Science B.V. All rights reserved.