Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, CA, USA.
Ophthalmology Department, Cochin Hospital and Université Paris Cité, Paris, France.
Stem Cells Transl Med. 2023 Nov 3;12(11):714-719. doi: 10.1093/stcltm/szad058.
Limbal stem cells (LSCs) are adult stem cells located at the limbus ensuring the continuous renewal of the corneal epithelium, critical to maintain an optimal visual function. Damages to the LSCs or their niche microenvironment lead to limbal stem cell deficiency (LSCD), a potentially blinding disease. Transplantation of LSCs as a treatment for severe to total LSCD has gained popularity since 1980s, owing to the clinical success of the first direct limbal autograft transplantation. Recent advances in the understanding of the LSCs' molecular identity and regulation have enabled preclinical and clinical advancements of promising LSCs therapies. However, lack of standardization of the diagnostic methods, staging of the disease severity, manufacturing process, and clinical outcome measures have hindered the advancement of the therapy. To move these therapies to the clinic, optimization and standardization of the diagnostic strategy, cell product manufacturing, and assessment of clinical efficacy with potency assays are key points to the development of customized therapies. Recent findings suggest that residual LSCs exist in eyes presenting with clinical signs of total LSCD, which opens new therapeutic strategies for eyes with partial LSCD. Prospective, randomized, multicentric controlled clinical trials are necessary to determine the efficacy of different LSCs therapies for different stages of LSCD using a set of standardized outcome measures.
角膜缘干细胞（limbal stem cells，LSCs）是位于角膜缘的成体干细胞，可确保角膜上皮的持续更新，对维持最佳视觉功能至关重要。LSCs 或其龛微环境的损伤会导致角膜缘干细胞缺乏症（limbal stem cell deficiency，LSCD），这是一种潜在的致盲性疾病。自 20 世纪 80 年代以来，由于首例直接角膜缘自体移植的临床成功，LSCs 移植作为严重至全部 LSCD 的治疗方法越来越受到关注。对 LSCs 分子特征和调控的深入了解，促进了有前途的 LSCs 治疗方法的临床前和临床进展。然而，由于缺乏诊断方法的标准化、疾病严重程度的分期、制造工艺和临床疗效评估方法的标准化，限制了该治疗方法的进展。为了将这些治疗方法推向临床，优化和标准化诊断策略、细胞产品制造以及使用效力测定评估临床疗效是开发定制治疗方法的关键点。最近的研究结果表明，在临床表现为完全 LSCD 的眼中存在残留的 LSCs，这为部分 LSCD 眼提供了新的治疗策略。需要前瞻性、随机、多中心对照临床试验，使用一组标准化的疗效评估方法，来确定不同阶段 LSCD 中不同 LSCs 治疗方法的疗效。
