Jones Melissa K, Lu Bin, Girman Sergey, Wang Shaomei
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA; David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave., Los Angeles, CA 90095, USA.
Prog Retin Eye Res. 2017 May;58:1-27. doi: 10.1016/j.preteyeres.2017.01.004. Epub 2017 Jan 19.
Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments.
基于细胞的疗法为治疗视网膜退行性疾病提供了多种选择，如年龄相关性黄斑变性（AMD）和视网膜色素变性（RP）。AMD具有遗传和环境风险因素，而RP主要是一种单基因疾病。虽然针对一些新生血管性AMD患者有治疗方法，但大多数视网膜退行性疾病患者没有有效的治疗手段，因此表明需要针对不同患者群体的通用疗法。两种主要的基于细胞的机制方法正在临床试验中进行测试。替代疗法利用细胞衍生的视网膜色素上皮（RPE）细胞来替代丢失或有缺陷的宿主RPE细胞。这些细胞在形态和功能上与天然RPE细胞相似，并且有可能在体内替代RPE的职责。保护疗法利用支持性细胞通过神经营养机制部分地帮助视觉功能和光感受器的保护。保护策略的目标是阻止或减缓疾病的进展并维持剩余的视觉功能。一些临床试验正在测试替代和保护细胞疗法在患者中的安全性；然而，疗效的衡量标准还需要进一步评估。此外，在未来的试验中需要解决许多关于移植细胞的免疫相关反应、寿命和功能的普遍关注问题。本综述将总结基于细胞的临床前和临床研究的现状，重点关注替代和保护策略以及这些类型治疗仍然存在的障碍。
