Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin
Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin
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DOI：
10.1038/nn1088
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发表时间：
2003-08-01
影响因子：
25
通讯作者：
Chen, DF
中科院分区：
文献类型：
--
作者：
Kinouchi, R;Takeda, M;Chen, DF
随着神经科学和干细胞研究的最新进展，神经移植已成为治疗中枢神经系统疾病的一种有前途的疗法。然而，移植的成功受到神经植入物存活和与宿主建立神经元连接的能力的限制。对于造成这种失败的机制知之甚少。神经植入引发反应性神经胶质增生，这一过程伴随着星形胶质细胞中中间丝的上调和星形胶质疤痕组织的形成。在这里，我们发现，成年小鼠的视网膜缺乏胶质原纤维酸性蛋白和波形蛋白，因此缺乏反应性星形胶质细胞和米勒细胞的中间丝，为移植神经元迁移和延伸神经突提供了宽松的环境。移植的细胞牢固地整合到宿主视网膜中，具有独特的神经元特性和适当的神经元投射。我们的结果表明反应性星形胶质细胞在防止移植后神经移植物整合中发挥重要作用。
With recent progress in neuroscience and stem-cell research, neural transplantation has emerged as a promising therapy for treating CNS diseases. The success of transplantation has been limited, however, by the restricted ability of neural implants to survive and establish neuronal connections with the host. Little is known about the mechanisms responsible for this failure. Neural implantation triggers reactive gliosis, a process accompanied by upregulation of intermediate filaments in astrocytes and formation of astroglial scar tissue. Here we show that the retinas of adult mice deficient in glial fibrillary acidic protein and vimentin, and consequently lacking intermediate filaments in reactive astrocytes and Muller cells, provide a permissive environment for grafted neurons to migrate and extend neurites. The transplanted cells integrated robustly into the host retina with distinct neuronal identity and appropriate neuronal projections. Our results indicate an essential role for reactive astroglial cells in preventing neural graft integration after transplantation.