Ocular Surface Regeneration by Limbal Stem Cells Therapies: State of the Art, Challenges, and Perspectives.
Ocular Surface Regeneration by Limbal Stem Cells Therapies: State of the Art, Challenges, and Perspectives.
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DOI：
10.1093/stcltm/szad058
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发表时间：
2023-11-03
影响因子：
6
通讯作者：
中科院分区：
文献类型：
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角膜缘干细胞（LSC）是位于利姆布斯的成体干细胞，其确保角膜上皮的持续更新，对于维持最佳视觉功能至关重要。对LSC或其生态位微环境的损害导致角膜缘干细胞缺乏症（LSCD），这是一种潜在的致盲疾病。自20世纪80年代以来，由于第一次直接角膜缘自体移植的临床成功，LSC移植作为严重至完全LSCD的治疗已经得到普及。对LSC的分子身份和调控的理解的最新进展使得有前景的LSC疗法的临床前和临床进展成为可能。然而，缺乏标准化的诊断方法，疾病严重程度的分期，制造工艺和临床结果的措施，阻碍了治疗的进步。为了将这些疗法推向临床，诊断策略的优化和标准化、细胞产品的制造以及用效价测定法评估临床疗效是开发定制疗法的关键点。最近的研究结果表明，残留的LSC存在于表现出完全LSCD临床体征的眼睛中，这为部分LSCD的眼睛开辟了新的治疗策略。前瞻性，随机，多中心对照临床试验是必要的，以确定不同的LSC治疗LSCD的不同阶段的疗效使用一套标准化的结果措施。LSC治疗的挑战和成功的关键。往返cGMP设施的运输、生产工艺以及由经过培训的操作员进行监测是需要优化和验证的关键点。移植前后LSC功能评价的标准化，以及符合cGMP和监管标准的移植物质量评价应成为当今的金标准。缩略语：AS-OCT：眼前节光学相干断层扫描; CLET：培养角膜缘上皮移植; cGMP：现行良好生产规范; IC：印模细胞学; IVCM：体内共聚焦显微镜; OR：手术室。
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. Challenges in LSCs therapy and key for success. Transport to and from the cGMP facility, manufacturing process, and monitoring by trained operators are key points requiring optimization and validation. Standardization of the evaluation of LSCs function before and after transplantation, and evaluation of graft quality in compliance with cGMP and regulatory standards should be the gold standard nowadays. Abbreviations: AS-OCT: anterior segment optical coherence tomogrpahy; CLET: cultivated limbal epithelial transplanation; cGMP: current good manufacturing practices; IC: impression cytology; IVCM: in vivo confocal microscopay; OR: operating room.
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DOI：
10.1089/ten.tec.2016.0388
发表时间：
2017-04
期刊：
Tissue engineering. Part C, Methods
影响因子：
--
作者：
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通讯作者：
Deng SX
影响因子：
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作者：
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影响因子：
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Dhubhghaill, Sorcha Ni
影响因子：
5.2
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影响因子：
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