Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, 20 College Road, The Academia, Discovery Tower Level 6, Singapore, 169856, Singapore.
Singapore National Eye Centre, Singapore, 168751, Singapore.
Stem Cell Res Ther. 2020 Dec 4;11(1):523. doi: 10.1186/s13287-020-02046-2.
The corneal endothelium located on the posterior corneal surface is responsible for regulating stromal hydration. This is contributed by a monolayer of corneal endothelial cells (CECs), which are metabolically active in a continuous fluid-coupled efflux of ions from the corneal stroma into the aqueous humor, preventing stromal over-hydration and preserving the orderly arrangement of stromal collagen fibrils, which is essential for corneal transparency. Mature CECs do not have regenerative capacity and cell loss due to aging and diseases results in irreversible stromal edema and a loss of corneal clarity. The current gold standard of treatment for this worldwide blindness caused by corneal endothelial failure is the corneal transplantation using cadaveric donor corneas. The top indication is Fuchs corneal endothelial dystrophy/degeneration, which represents 39% of all corneal transplants performed. However, the global shortage of transplantable donor corneas has restricted the treatment outcomes, hence instigating a need to research for alternative therapies. One such avenue is the CEC regeneration from endothelial progenitors, which have been identified in the peripheral endothelium and the adjacent transition zone. This review examines the evidence supporting the existence of endothelial progenitors in the posterior limbus and summarizes the existing knowledge on the microanatomy of the transitional zone. We give an overview of the isolation and ex vivo propagation of human endothelial progenitors in the transition zone, and their growth and differentiation capacity to the corneal endothelium. Transplanting these bioengineered constructs into in vivo models of corneal endothelial degeneration will prove the efficacy and viability, and the long-term maintenance of functional endothelium. This will develop a novel regenerative therapy for the management of corneal endothelial diseases.
角膜内皮位于后角膜表面，负责调节基质的水化。这是由一层角膜内皮细胞（CEC）完成的，这些细胞在代谢上是活跃的，它们将离子从角膜基质连续不断地泵出到房水中，从而防止基质过度水化，并维持基质胶原纤维的有序排列，这对角膜透明性至关重要。成熟的 CEC 没有再生能力，由于衰老和疾病导致的细胞丢失会导致不可逆的基质水肿和角膜清晰度丧失。目前，针对由角膜内皮功能衰竭引起的这种全球失明的治疗金标准是使用尸体供体角膜进行角膜移植。最主要的适应证是 Fuchs 角膜内皮营养不良/变性，占所有角膜移植的 39%。然而，全球可用于移植的供体角膜短缺限制了治疗效果，因此需要研究替代疗法。其中一种方法是从内皮祖细胞中再生 CEC，这些内皮祖细胞已在周边内皮和相邻的过渡区中被发现。这篇综述检查了支持后缘部存在内皮祖细胞的证据，并总结了过渡区的微观解剖学的现有知识。我们概述了人内皮祖细胞在过渡区的分离和体外培养，以及它们向角膜内皮生长和分化的能力。将这些生物工程构建体移植到角膜内皮变性的体内模型中，将证明其功效和可行性，以及功能性内皮的长期维持。这将为角膜内皮疾病的管理开发一种新的再生治疗方法。
