To evaluate the effectiveness of cultured human limbal epithelium for the treatment of limbal stem cell deficiency

角膜是眼睛前部的透明窗口，它的清晰度对于光线传输到眼睛后部以获得视觉感知至关重要。角膜的透明度取决于其最外层的上皮细胞的完整性，在一生中，上皮细胞由角膜边缘的一群干细胞再生，该区域被称为角膜缘，即所谓的角膜缘干细胞(LSC)。如果LSC因损伤或疾病而变得缺乏，这种上皮细胞就会破裂，导致剧烈的疼痛和失明。这种情况通常很难治疗，然而，角膜缘干细胞缺乏症(LSCD)的治疗得益于近年来的重大突破。取自患者的LSC？S本人(单眼病)或相对健康的眼或身体眼可在实验室培养，然后移植到患病眼。然而，这项技术使用动物产品来帮助培养具有极大疾病传播风险的细胞。此外，由于治疗的多样性和报告的病例数量很少，这种治疗的安全性和有效性很难确定。因此，在正式的结构化临床试验确定其有效性和安全性之前，不能承认培养的角膜缘上皮移植，从而为NHS提供资金。这样的试验构成了这项提案的主要目标。因此，我们开发了一种不含动物产品的产品。在实验室的超清洁环境中培养细胞的技术，成功地将8名LSCD患者的一只眼移植到了他们健康的另一只眼的LSC。尽管我们取得了成功，但对于得出正确的结论来说，这个患者数量并不重要。因此，这项建议旨在通过治疗更多的完全性单侧LSCD患者来评估我们的方法的安全性和有效性。该项目的另一个目标是开发培养的人类LSC的冷冻方法以供储存，并建立一项服务，以提供临床级别的培养的LSC供英国其他中心移植。此外，这项研究将调查LSCD患者的泪膜异常，以便进行个性化的眼部治疗。最后，LSCD对患者S的生活质量产生了巨大的影响，严重影响了生产力和休闲活动。为此，我们选择了4份问卷，以了解LSCD患者及其治疗的不同方面。

The cornea is the clear window at the front of the eye and its clarity is vital for light transmission to the back of the eye for visual perception. Transparency of the cornea depends upon the integrity of its outermost layer called the epithelium, which is constantly regenerated throughout life by a population of stem cells found at the edge of the cornea in an area called the limbus, the so called limbal stem cells (LSC). If LSC becomes deficient as a result of injury or disease, this epithelium will breakdown leading to severe pain and blindness. This condition is often difficult to treat, however, the management of limbal stem cell deficiency (LSCD) has benefited from major breakthroughs in recent years. LSC from the patient?s own (one eye disease) or a relative healthy eye or from a cadaveric eye can grow in the laboratory and then transplanted to the diseased eye. This technique however uses animal products to help grow the cells with a great risk of diseases transmission. In addition, the safety and effectiveness of this treatment is rather difficult to establish due to the diversity and the small number of cases reported. Transplantation of cultured limbal epithelium can therefore not be recognized, enabling NHS funding, until its effectiveness and safety is determined by a formally structured clinical trial. Such a trial forms the main objective of this proposal. We have therefore developed an ?animal product free? technique for growing the cells in the laboratory in an ultra-clean environment and successfully transplanted 8 patients with LSCD in one eye by taking LSC from their healthy other eye. Despite of our success, this number of patients is not significant to draw proper conclusions. This proposal aims therefore to evaluate the safety and efficacy of our methods by treating more patients with total unilateral LSCD. Another aim of the project is to develop a freezing method of cultured human LSC for storage and to set-up a service to supply clinical grade cultured LSC for transplantation at other UK centres. In addition, this study will investigate the abnormal tear film in patients with LSCD to allow for a customised eye treatment. Finally, LSCD has an enormous impact on patient?s quality of life with serious detrimental effects on productivity and leisure activities. To that effect we have selected 4 questionnaires to look at different aspects of patients with LSCD and its treatment.