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从干细胞生态位环境到角膜上皮组织工程。

From stem cell niche environments to engineering of corneal epithelium tissue.

机构信息

Taipei Eye Center, 2F, 350 Section 4, ChengKung Road, Taipei 114, Taiwan,

出版信息

Jpn J Ophthalmol. 2014 Mar;58(2):111-9. doi: 10.1007/s10384-014-0306-8. Epub 2014 Feb 5.

Abstract

Studies on stem cells (SC) show that SC functions are determined by the extracellular microenvironment, known as the "niche", and by intrinsic genetic programs in the SCs; both are involved in regulating the delicate balance of self-renewal and differentiation. We have identified an animal model of limbal SC (LSC) deficiency and transplantation of SC-containing limbal tissue to treat the LSC deficiency, which could not only replace LSCs by providing new healthy corneal epithelial cells but also restore the lost niche of the limbal stromal layer, causing the regression of vessels and rearrangement of the corneal stromal lamellae. The purpose of the ex-vivo expansion technique is to develop a method that will enable culture of a small number of SCs which could than be expanded in a defined cultured system while preserving the original characteristics and properties of the SCs. In addition, SC characteristics will continue to be maintained when the cultured cells are transplanted back into the host. Bromodeoxyuridine-retaining, ΔNp63, ABCG2, p120, and N-cadherin immunoreactive studies of LSC cultured on an amniotic membrane have been performed. Pathological studies have been conducted for cases with preexisting central corneal stromal opacity treated by transplantation of LSCs followed by penetrating keratoplasty. The results indicate that the amniotic membrane can provide the niche environment for cultured LSCs and maintain the limbal-like environment for the transplanted area of cornea.

摘要

干细胞(SC)的研究表明,SC 功能取决于细胞外微环境,即所谓的“龛位”,以及 SC 中的内在遗传程序;两者都参与调节自我更新和分化的微妙平衡。我们已经确定了一种角膜缘干细胞(LSC)缺陷的动物模型,以及含有 SC 的角膜缘组织移植来治疗 LSC 缺陷,这不仅可以通过提供新的健康角膜上皮细胞来替代 LSCs,还可以恢复丢失的角膜缘基质层龛位,导致血管消退和角膜基质板层的重新排列。体外扩增技术的目的是开发一种方法,使少量 SC 能够在一个定义的培养系统中进行扩增,同时保持 SC 的原始特征和性质。此外,当培养细胞被移植回宿主时,SC 特性将继续保持。对培养在羊膜上的 LSC 进行了溴脱氧尿苷保留、ΔNp63、ABCG2、p120 和 N-钙粘蛋白免疫反应研究。对接受 LSC 移植后继行穿透性角膜移植术治疗的原有中央角膜基质混浊病例进行了病理研究。结果表明,羊膜可以为培养的 LSC 提供龛位环境,并维持移植角膜区域的类似角膜缘环境。

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