Department of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California CA, USA.
USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California CA, USA.
Curr Stem Cell Res Ther. 2022;17(3):214-225. doi: 10.2174/1574888X16666210804112104.
The main cause of progressive vision impairment in retinal degenerative diseases is the dysfunction of photoreceptors and the underlying retinal pigment epithelial cells. The inadequate regenerative capacity of the neural retina and lack of established therapeutic options demand the development of clinical-grade protocols to halt the degenerative process in the eye or replace the damaged cells by using stem cell-derived products. Recently, stem cell-based regenerative therapies have been at the forefront of clinical investigations for retinal dystrophies.
This article will review different stem cell-based therapies currently employed for retinal degenerative diseases, recent clinical trials, and major challenges in the translation of these therapies from bench to bedside.
A systematic literature review was conducted to identify potentially relevant articles published in MEDLINE/PubMed, Embase, ClinicalTrials.gov, Drugs@FDA, European Medicines Agency, and World Health Organization International Clinical Trials Registry Platform.
Transplantation of healthy cells to replace damaged cells in the outer retina is a clinically relevant concept because the inner retina that communicates with the visual areas of the brain remains functional even after the photoreceptors are completely lost. Various methods have been established for the differentiation of pluripotent stem cells into different retinal cell types that can be used for therapies. Factors released from transplanted somatic stem cells showed trophic support and photoreceptor rescue during the early stages of the disease. Several preclinical and phase I/II clinical studies using terminally differentiated photoreceptor/retinal pigment epithelial cells derived from pluripotent stem cells have shown proof of concept for visual restoration in Age-related Macular Degeneration (AMD), Stargardt disease, and Retinitis Pigmentosa (RP).
Cell replacement therapy has great potential for vision restoration. The results obtained from the initial clinical trials are encouraging and indicate its therapeutic benefits. The current status of the therapies suggests that there is a long way to go before these results can be applied to routine clinical practice. Input from the ongoing multicentre clinical trials will give a more refined idea for the future design of clinical-grade protocols to transplant GMP level HLA matched cells.
视网膜退行性疾病导致视力进行性损害的主要原因是光感受器和底层视网膜色素上皮细胞的功能障碍。神经视网膜的再生能力不足和缺乏既定的治疗选择，这就要求制定临床级别的方案，以阻止眼睛中的退行性过程或用干细胞衍生产品替代受损细胞。最近，基于干细胞的再生疗法一直是视网膜营养不良临床研究的前沿。
本文将综述目前用于视网膜退行性疾病的不同基于干细胞的疗法、最近的临床试验以及将这些疗法从实验室转化为临床应用所面临的主要挑战。
系统地检索了 MEDLINE/PubMed、Embase、ClinicalTrials.gov、Drugs@FDA、欧洲药品管理局和世界卫生组织国际临床试验注册平台上发表的潜在相关文章，以确定可能相关的文章。
将健康细胞移植到外视网膜以替代受损细胞是一种具有临床意义的概念，因为与大脑视觉区域相连的内视网膜即使在光感受器完全丧失后仍保持功能。已经建立了各种方法，可将多能干细胞分化为不同的视网膜细胞类型，用于治疗。移植的体干细胞释放的因子在疾病的早期阶段表现出营养支持和光感受器挽救作用。使用多能干细胞衍生的终末分化光感受器/视网膜色素上皮细胞进行的几项临床前和 I/II 期临床试验已经证明了在年龄相关性黄斑变性（AMD）、斯塔加特病和色素性视网膜炎（RP）中恢复视力的概念验证。
细胞替代疗法具有恢复视力的巨大潜力。初步临床试验的结果令人鼓舞，表明其具有治疗益处。目前的治疗方法表明，在这些结果可以应用于常规临床实践之前，还有很长的路要走。正在进行的多中心临床试验的结果将为移植符合 GMP 标准的 HLA 匹配细胞的临床级方案的未来设计提供更精确的思路。
