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人角膜缘上皮干细胞体外扩增的评价。

Critical appraisal of ex vivo expansion of human limbal epithelial stem cells.

机构信息

Research and Development Department, Tissue Tech, Inc., and Ocular Surface Center Miami, FL, USA.

出版信息

Curr Mol Med. 2010 Dec;10(9):841-50. doi: 10.2174/156652410793937796.

DOI:10.2174/156652410793937796
PMID:21091422
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3190238/
Abstract

The stem cells (SCs) of the corneal epithelium located in the limbal basal layer are the ultimate source to maintain corneal epithelial homeostasis. Like other adult tissue-specific SCs, self renewal and fate decision of limbal SCs are regulated by a specialized in vivo microenvironment, termed "niche". Loss of limbal SCs or dysfunction of the limbal niche renders corneas with a unique clinical disease labeled limbal stem cell deficiency (LSCD). Besides transplantation of autologous or allogeneic limbal SCs or amniotic membrane, a new strategy of treating LSCD is to transplant a bio-engineered graft by expanding limbal SCs ex vivo. Herein, we conduct a critical appraisal of six protocols that have successfully been practiced in treating human patients with LSCD, and identify issues whether niche regulation has been disrupted or maintained during isolation and expansion. Consequently, we propose a future direction that may circumvent the potential pitfalls existing in these conventional protocols by preserving the interaction between limbal SCs and their native niche cells during isolation and expansion. Such an approach may one day help realize considerable promise held by adult SCs in treating a number of diseases.

摘要

角膜上皮的干细胞(SCs)位于角膜缘基底层,是维持角膜上皮内稳态的最终来源。与其他成人组织特异性SCs 一样,角膜缘SCs 的自我更新和命运决定受称为“龛位”的专门体内微环境调控。角膜缘SCs 的丧失或角膜缘龛位的功能障碍会导致角膜出现一种独特的临床疾病,称为角膜缘干细胞缺乏症(LSCD)。除了自体或同种异体角膜缘干细胞移植或羊膜移植外,治疗 LSCD 的新策略是通过体外扩增角膜缘SCs 移植生物工程移植物。在此,我们对已成功应用于治疗 LSCD 人类患者的六种方案进行了批判性评估,并确定了在分离和扩增过程中龛位调节是否被破坏或维持的问题。因此,我们提出了一个未来的方向,即在分离和扩增过程中保留角膜缘SCs 与其天然龛位细胞之间的相互作用,从而避免这些传统方案中存在的潜在陷阱。这种方法可能有一天有助于实现成人SCs 在治疗多种疾病方面的巨大潜力。

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本文引用的文献

1
Greater growth potential of p63-positive epithelial cell clusters maintained in human limbal epithelial sheets.维持在人角膜缘上皮片中的p63阳性上皮细胞簇具有更大的生长潜力。
Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4611-7. doi: 10.1167/iovs.08-2586. Epub 2009 Mar 25.
2
The use of human mesenchymal stem cell-derived feeder cells for the cultivation of transplantable epithelial sheets.使用人骨髓间充质干细胞来源的饲养层细胞培养可移植上皮片。
Invest Ophthalmol Vis Sci. 2009 May;50(5):2109-15. doi: 10.1167/iovs.08-2262. Epub 2009 Jan 10.
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Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells.角膜缘微环境可诱导毛囊干细胞转分化为角膜上皮样细胞。
Stem Cells. 2009 Mar;27(3):642-52. doi: 10.1634/stemcells.2008-0721.
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Minimal conjunctival limbal autograft for total limbal stem cell deficiency.微小结膜角膜缘自体移植治疗全角膜缘干细胞缺乏症
Cornea. 2008 Jul;27(6):730-3. doi: 10.1097/QAI.0b013e31815cea8b.
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Limbal epithelial crypt: a model for corneal epithelial maintenance and novel limbal regional variations.角膜缘上皮隐窝:角膜上皮维持及角膜缘新区域变异的模型
Arch Ophthalmol. 2008 May;126(5):665-9. doi: 10.1001/archopht.126.5.665.
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A novel NIH/3T3 duplex feeder system to engineer corneal epithelial sheets with enhanced cytokeratin 15-positive progenitor populations.一种新型的NIH/3T3双相饲养层系统,用于构建具有增强的细胞角蛋白15阳性祖细胞群体的角膜上皮片。
Tissue Eng Part A. 2008 Jul;14(7):1275-82. doi: 10.1089/ten.tea.2007.0212.
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Sutureless amniotic membrane transplantation for partial limbal stem cell deficiency.无缝线羊膜移植治疗部分角膜缘干细胞缺乏症
Am J Ophthalmol. 2008 May;145(5):787-94. doi: 10.1016/j.ajo.2008.01.009. Epub 2008 Mar 10.
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Air exposure induced squamous metaplasia of human limbal epithelium.空气暴露诱导人角膜缘上皮发生鳞状化生。
Invest Ophthalmol Vis Sci. 2008 Jan;49(1):154-62. doi: 10.1167/iovs.07-0883.
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Proteomic analysis of epithelium-denuded human amniotic membrane as a limbal stem cell niche.作为角膜缘干细胞微环境的去上皮人羊膜的蛋白质组学分析。
Mol Vis. 2007 Sep 18;13:1711-21.
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Characterization of extracellular matrix components in the limbal epithelial stem cell compartment.角膜缘上皮干细胞区室中细胞外基质成分的特征分析。
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