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模拟人角膜内皮细胞微环境诱导人胚胎干细胞分化为角膜内皮细胞的研究进展
孙琳
吴欣怡 [综述]
作者及单位信息
·
DOI： 10.3760/cma.j.issn.2095-0160.2015.09.017
Advances in differentiation of human embryonic stem cells into corneal endothelial cells under the mimical microenvironment
Sun Lin
Wu Xinyi
Authors Info & Affiliations
Sun Lin
Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan 250012, China
Wu Xinyi
·
DOI： 10.3760/cma.j.issn.2095-0160.2015.09.017
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摘要

角膜内皮供体不足成为开展角膜内皮移植等手术的主要问题，生物工程角膜为角膜内皮移植的开展提供了解决途径。人胚胎干细胞(ESCs)诱导分化出功能性角膜内皮细胞后可以在一定程度上缓解角膜供体不足，尤其是角膜内皮供应不足的现状。目前理想可行的方法是体外模拟角膜内皮细胞的发育过程，将人ESCs诱导分化为神经嵴干细胞(NCSCs)，再利用生长因子和细胞外基质构建细胞生长的微环境，制备适当的条件培养基以诱导NCSCs分化为角膜内皮细胞。目前NCSCs相关的诱导机制尚不十分清楚，有待进一步研究。本文就微环境对角膜内皮细胞发育过程的影响，以及诱导人ESCs分化为角膜内皮细胞等方面的研究进展进行综述。

人;胚胎干细胞;神经嵴干细胞;角膜内皮细胞;分化
ABSTRACT

The lack of donor corneal endothelium is a serious impediment to the development of corneal endothelial transplantation, whereas the bioengineered cornea provides an approach to this problem. Functional corneal endothelial cells which differentiated from human embryonic stem cells (ESCs) can, to some extent, relieve the lack of donor corneas, especially for corneal endothelia. At the moment, an optimal way of offering bioengineered-corneal endothelium is to cultivate the corneal endothelial cells in vitro. This is a process of inducing human ESCs to differentiate into neural crest stem cells (NCSCs) and then into corneal endothelial cells in a favorable medium with growth factors and extracellular matrix, which are matched microenvironment of endothelial cells in vitro. However, the inducement condition is still pending and remains for further research. This article reviewed the researching development of bioengineered-corneal endothelium from the effect of microenvironment and the induction of human ESCs.

Human;Embryonic stem cells;Neural crest stem cell;Endothelium, corneal;Differentiation
Wu Xinyi, Email: mocdef.3ab618688uwyx
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引用本文

孙琳,吴欣怡. 模拟人角膜内皮细胞微环境诱导人胚胎干细胞分化为角膜内皮细胞的研究进展[J]. 中华实验眼科杂志,2015,33(9)：844-847.

DOI:10.3760/cma.j.issn.2095-0160.2015.09.017

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角膜病是全球和中国第二位致盲眼病 [ 1 , 2 ]，角膜移植是治疗严重角膜病的常用方法，中国供体角膜匮乏，因此角膜移植手术比例不足1.3% [ 3 ]。角膜内皮病变为严重的可致盲角膜疾病之一。角膜内皮由单层细胞构成，角膜内皮细胞无增生能力，故细胞数目随年龄的增长而逐渐减少，此外也可受到多种因素的损伤，出现内皮功能失代偿，形成大泡性角膜病变，最终出现视力障碍 [ 4 ]。角膜内皮移植术为治疗角膜内皮病变和内皮失代偿的首选术式，但目前供体角膜内皮来源缺乏，严重阻碍了该技术的临床应用 [ 5 , 6 ]。寻找新的细胞来源以构建生物工程角膜是目前研究的热点之一。骨髓间充质干细胞可以诱导分化为角膜内皮细胞，但其更易向骨细胞、软骨细胞和脂肪细胞等中胚层细胞分化，而跨胚层分化为角膜内皮细胞相对困难，分化效率较低 [ 7 ]。血管内皮细胞也可作为角膜内皮细胞的替代物，但动物实验结果并不理想 [ 8 ]，主要问题是植片上的血管内皮细胞排列不规则，缺乏典型的六边形结构，部分植片中存活的细胞数目不足。同时由于血管内皮细胞泵功能较差，影响角膜的透明度。Thomson等 [ 9 ]证明人胚胎干细胞(embryonic stem cells，ESCs)具有无限的自我更新能力及多向分化潜能，因此将ESCs诱导分化为功能性角膜内皮细胞是一种理想的构建生物工程角膜内皮的方法。
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备注信息
A
吴欣怡，Email： mocdef.3ab618688uwyx
B
国家自然科学基金项目 (81271716)
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