Limbal Stem Cell Laboratory, Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Ocul Surf. 2009 Jul;7(3):128-44. doi: 10.1016/s1542-0124(12)70308-7.
Corneal neovascularization (CNV) associated with severe limbal stem cell (LSC) deficiency remains a challenging ocular surface disease in that corneal inflammation may persist and progress, and the condition will not improve without LSC transplantation. A prominent feature after successful LSC transplantation is the suppression of corneal inflammation and CNV, which is generally attributed to the endogenous anti-angiogenic/anti-inflammatory factors secreted by corneal epithelial cells. In addition, corneal epithelial basement membrane (EBM) plays a unique role in the regulation of angiogenesis; several potent anti-angiogenic factors are derived from the matrix component of EBM, such as endostatin (from collagen XVIII) and restin (from collagen XV). Also, angio-inhibitory thrombospondin and tissue inhibitor of metalloproteinase-3 are deposited in EBM. Moreover, the heparan sulphate proteoglycan in EBM can bind and sequester VEGF and FGF-2 from activation. Recently, cultivated corneal epithelial transplantation (CCET) and cultivated oral mucosal epithelial transplantation (COMET) have emerged as promising techniques for the treatment of LSC deficiency. When human limbo-corneal epithelial (HLE) cells are cultivated on cryopreserved amniotic membrane, production of endostatin, restin, and IL-1ra is enhanced. This highlights the significance of delicate epithelial-matrix interactions in the generation of anti-angiogenic/anti-inflammatory factors by HLE cells, and this may, in part, explain the rapid restoration of corneal avascularity following CCET. In addition, whether epithelial stem cells can persist after transplantation is the key for CCET and COMET. Emerging evidence of long-term survival of cultivated epithelial cells after transplantation suggest that epithelial stem cells can be isolated and cultivated in vitro, and can re-establish the epithelial phenotype in vivo. Taken together, the merits of enhanced anti-angiogenic activity and the preservation of corneal epithelial stem cells encourage further application of this tissue engineering technique for ocular surface reconstruction.
角膜新生血管（CNV）与严重的角膜缘干细胞（LSC）缺乏症有关，是一种具有挑战性的眼表疾病，因为如果不进行 LSC 移植，角膜炎症可能会持续并进展，病情也不会改善。LSC 移植成功后的一个显著特征是抑制角膜炎症和 CNV，这通常归因于角膜上皮细胞分泌的内源性抗血管生成/抗炎因子。此外，角膜上皮基底膜（EBM）在调节血管生成方面起着独特的作用；几种有效的抗血管生成因子来源于 EBM 的基质成分，如内皮抑素（来自胶原 XVIII）和 restin（来自胶原 XV）。此外，血管抑制性血小板反应蛋白和金属蛋白酶组织抑制剂-3 沉积在 EBM 中。此外，EBM 中的硫酸乙酰肝素蛋白聚糖可以结合和隔离 VEGF 和 FGF-2 以防止其激活。最近，培养的角膜上皮移植（CCET）和培养的口腔黏膜上皮移植（COMET）已成为治疗 LSC 缺乏症的有前途的技术。当人角膜缘上皮（HLE）细胞在冷冻保存的羊膜上培养时，内皮抑素、restin 和 IL-1ra 的产量增加。这突出了上皮-基质相互作用在 HLE 细胞产生抗血管生成/抗炎因子中的重要性，这在一定程度上可以解释 CCET 后角膜迅速恢复无血管状态的原因。此外，上皮干细胞在移植后是否能持续存在是 CCET 和 COMET 的关键。培养的上皮细胞移植后长期存活的新证据表明，上皮干细胞可以在体外分离和培养，并能在体内重新建立上皮表型。综上所述，增强抗血管生成活性和保留角膜上皮干细胞的优点鼓励进一步应用这种组织工程技术进行眼表面重建。
