Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs.
Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs.
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DOI：
10.1038/ncomms5047
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发表时间：
2014-06-10
影响因子：
16.6
通讯作者：
Canto-Soler, M. Valeria
中科院分区：
文献类型：
--
作者：
Zhong, Xiufeng;Gutierrez, Christian;Xue, Tian;Hampton, Christopher;Vergara, M. Natalia;Cao, Li-Hui;Peters, Ann;Park, Tea Soon;Zambidis, Elias T.;Meyer, Jason S.;Gamm, David M.;Yau, King-Wai;Canto-Soler, M. Valeria
许多形式的失明是由视网膜光感受器的功能障碍或丧失引起的。诱导性多能干细胞（iPSC）在这些疾病的建模或作为潜在的治疗剂方面具有巨大的潜力。然而，为了实现这一承诺，剩下的挑战是诱导人iPSC在体外重建天然视网膜的关键结构和功能特征，特别是具有外节盘和光敏性的光感受器的存在。在这里，我们报告说，hiPSC可以，在一个高度自主的方式，recapitulate在体内观察到的视网膜发育的每个主要步骤的时空，并形成三维视网膜杯，包含所有主要的视网膜细胞类型排列在其适当的层。此外，我们的hiPSC衍生的视网膜组织中的光感受器实现了高级成熟，显示了外节盘形成和光敏性的开始。这一成功使我们更接近hiPSC用于疾病建模的预期用途，并为未来的治疗开辟了可能性。
Many forms of blindness result from the dysfunction or loss of retinal photoreceptors. Induced pluripotent stem cells (iPSC) hold great potential for the modeling of these diseases or as potential therapeutic agents. However, to fulfill this promise, a remaining challenge is to induce human iPSC to recreate in vitro key structural and functional features of the native retina, in particular the presence of photoreceptors with outer-segment discs and light-sensitivity. Here we report that hiPSC can, in a highly autonomous manner, recapitulate spatiotemporally each of the main steps of retinal development observed in vivo and form 3-dimensional retinal cups that contain all major retinal cell types arranged in their proper layers. Moreover, the photoreceptors in our hiPSC-derived retinal tissue achieve advanced maturation, showing the beginning of outer-segment-disc formation and photosensitivity. This success brings us one step closer to the anticipated use of hiPSC for disease modeling and open possibilities for future therapies.
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