iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice.
iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal-Degeneration Mice.
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DOI：
10.1016/j.stemcr.2016.12.008
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发表时间：
2017-01-10
影响因子：
5.9
通讯作者：
Takahashi M
中科院分区：
文献类型：
--
作者：
Mandai M;Fujii M;Hashiguchi T;Sunagawa GA;Ito SI;Sun J;Kaneko J;Sho J;Yamada C;Takahashi M
最近在功能障碍性视网膜中通过光感受器前体移植进行功能恢复的成功已经导致对使用胚胎干细胞（ESC）或诱导多能干细胞（iPSC）衍生的视网膜祖细胞来治疗视网膜变性的兴趣增加。然而，对于已经失去外核层（ONL）的终末期退行性视网膜的基于细胞的疗法仍然是一个巨大的挑战。在本研究中，通过移植小鼠iPSC衍生的视网膜组织，在终末期视网膜变性模型（rd 1）中，我们通过基因标记观察到宿主双极细胞末端与移植物光感受器突触前末端之间的直接接触，在移植rd 1小鼠中显示出光响应行为，并使用多电极阵列系统通过离体微视网膜电描记术和神经节细胞记录来记录来自具有移植物的宿主视网膜的反应。我们的数据为移植ESC/iPSC视网膜以恢复终末期视网膜变性的视力提供了概念证明。iPSC视网膜重建终末期视网膜中的外核层。观察宿主双极细胞和移植物光感受器之间的接触。在iPSC-视网膜移植后，rd 1小鼠变得对光有反应。在移植后，从宿主rd 1视网膜记录RGC对光的反应。Mandai及其同事表明，iPSC视网膜可以在终末期变性视网膜（rd 1）中发育有组织的感光层。在移植后与宿主视网膜细胞可视化接触。这些移植小鼠表现出光反应行为，并且从宿主视网膜和向大脑发送输出信号的宿主视网膜神经节细胞记录光反应。
Recent success in functional recovery by photoreceptor precursor transplantation in dysfunctional retina has led to an increased interest in using embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal progenitors to treat retinal degeneration. However, cell-based therapies for end-stage degenerative retinas that have lost the outer nuclear layer (ONL) are still a big challenge. In the present study, by transplanting mouse iPSC-derived retinal tissue (miPSC retina) in the end-stage retinal-degeneration model (rd1), we visualized the direct contact between host bipolar cell terminals and the presynaptic terminal of graft photoreceptors by gene labeling, showed light-responsive behaviors in transplanted rd1 mice, and recorded responses from the host retina with transplants by ex vivo micro-electroretinography and ganglion cell recordings using a multiple-electrode array system. Our data provides a proof of concept for transplanting ESC/iPSC retinas to restore vision in end-stage retinal degeneration. iPSC retina reconstructs outer nuclear layer in the end-stage retina Contacts between the host bipolar cells and graft photoreceptors were visualized rd1 mice became responsive to light after iPSC-retina transplantation RGC responses to light were recorded from host rd1 retina after transplantation In this article, Mandai and colleagues showed that iPSC retina could develop organized photoreceptor layers in the end-stage degeneration retina (rd1) after transplantation with visualized contact with host retinal cells. These transplanted mice showed light-responsive behaviors, and light responses were recorded from the host retina and host retinal ganglion cells that send output signals to the brain.