Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases.
Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases.
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DOI：
10.1016/j.preteyeres.2017.01.004
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发表时间：
2017-05
影响因子：
17.8
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Jones MK;Lu B;Girman S;Wang S
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既有遗传危险因素，又有环境危险因素，而RP主要是单基因疾病。虽然一些新生血管性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方法，因此需要针对不同的患者群体进行通用治疗。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。替代疗法利用细胞来源的视网膜色素上皮(RPE)细胞来替代丢失或缺陷的宿主RPE细胞。这些细胞在形态和功能上与天然的RPE细胞相似，有可能取代RPE在体内的作用。保存疗法利用支持细胞来辅助视觉功能和光感受器的保存，部分是通过神经营养机制。保存策略的目标是阻止或减缓疾病的发展，并保持剩余的视觉功能。一些临床试验正在测试替代和保存细胞疗法在患者中的安全性；然而，疗效的衡量标准将需要进一步评估。此外，关于移植细胞的免疫相关反应、寿命和功能的一些普遍关注的问题将在未来的试验中得到解决。这篇综述将总结基于细胞的临床前和临床研究的现状，重点是替换和保存策略以及关于这些类型的治疗仍然存在的障碍。
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.