Nature：重大突破！科学家利用人类iPS细胞重建眼部角膜组织功能（附原文）

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2016年7月4日 讯 /生物谷BIOON/ --近日，刊登于国际杂志Nature上的一项研究报告中，来自大阪大学医学院的科学家们通过研究开发了一种2D培养系统，该系统可以通过促进人类诱导多能干细胞（iPS细胞）的自发分化来模拟整个眼睛的发育过程。. Z( S3 l9 [6 I$ C

, e- @' [  e* `7 r. p! p, D/ |过去研究中，研究者仅仅描述了一种特殊技术可以产生眼睛后部分，即视网膜、视网膜色素上皮细胞等；而本文中研究者开发的这种新技术能够同时产生眼睛的前部分（角质层和晶状体等）和后部分（视网膜和视网膜色素上皮细胞等），而这项研究发现属世界首次。4 k6 N% ~& _$ E( c

, A. K5 d- |& ]严重的角膜上皮疾病往往会导致失明，科学家们常常利用供体的角膜来对患者进行角膜移植，但如今这种疗法由于供体的缺少以及排斥反应的产生不断受阻，而患者的治疗或会面临多种阻碍。过去科学家们没有开发出新技术来诱导人类iPS细胞分化成为角膜上皮细胞和离体细胞从而制造功能性的角膜上皮组织。  D  q* m* a3 K7 J8 ~( }1 A/ r
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本文研究中，研究者开发的新型培养系统可以利用人类iPS细胞来产生一种2维的结构，这种结构是一种自发形成的外胚层多重区域（SEAM），其包括4个细胞的同心区；在发育期间组成眼睛的大部分群体细胞都是在SEAM的特殊位置形成的，比如角膜上皮细胞、视网膜细胞以及晶状体的上皮细胞等。: C  C* j; ^, i1 V
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本文研究中，研究者从SEAM的第三个区域中成功分离到了角膜上皮祖细胞，从而成功地制造出了功能性的角膜上皮组织。同时研究者通过将其移植到动物模型中进行研究，证实了人类iPS细胞形成的角膜上皮组织的治疗效力。; s, d+ b4 K) D7 R$ b
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相关研究结果或帮助科学家们利用人类iPS细胞来重建眼部的角膜上皮组织，而后期SEAM或可潜在地推动新技术的发展来重建眼部的角膜组织和其它部分，对于有效治疗眼部疾病的患者或将是一大福利。
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3楼原文 感谢nichifanlema2 提供8 E- x8 c% _2 _
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5楼详细介绍

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Co-ordinated ocular development from human iPS cells and recovery of corneal function 0 z) b% W. {. v5 J9 b2 {& P

) U% f- s3 A4 y7 ~2 E* m$ ERyuhei Hayashi, Yuki Ishikawa, Yuzuru Sasamoto, Ryosuke Katori, Naoki Nomura, Tatsuya Ichikawa, Saori Araki, Takeshi Soma, Satoshi Kawasaki, Kiyotoshi Sekiguchi, Andrew J. Quantock, Motokazu Tsujikawa & Kohji Nishida" L, B6 E" [- n0 h: A4 R

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The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells1, 2, 3, 4, 5. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells6, 7, 8, 9. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.- ?2 S# o9 _( `$ M