Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years
Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years
复制标题
DOI：
10.1167/iovs.15-18681
复制
发表时间：
2016-04-01
影响因子：
4.4
通讯作者：
Nagiel, Aaron
中科院分区：
文献类型：
--
作者：
Schwartz, Steven D.;Tan, Gavin;Nagiel, Aaron
在美国，晚期黄斑变性是导致视力丧失的一个重要原因，有超过200万人受到这种疾病的影响。尽管湿性AMD新疗法的开发取得了实质性进展，但干性AMD或Stargardt病中与地理萎缩相关的严重视力损害仍然无法治疗。最近，两项涉及18例这些疾病患者的I/II期研究表明，可以安全地植入人胚胎干细胞衍生的RPE (hESC-RPE)，以试图挽救光感受器和视觉功能。解剖和功能的结果是令人鼓舞的，超过一半的治疗患者的视力持续改善，并显示可能的细胞植入的证据。然而，由于随访时间相对较短，缺乏正式的对照组，初始视力差，患者人数少，任何结论都有待验证。除了一例术后感染性眼内炎外，在最初的18例患者中，没有发现与细胞治疗相关的不良事件，如增生、致瘤性或排斥反应相关的炎症。这些首次人体安全性研究为未来的研究打开了大门，包括招募不太晚期的患者，治疗其他导致RPE丧失的疾病，采用更短的免疫抑制方案，以及使用RPE移植的替代策略，如带或不带支架的细胞片来模拟Bruch膜。这些初步安全性研究的最终目标是促进将复杂的生物疗法持续转化为有意义的治疗策略，以解决未满足的医疗需求。
Advanced macular degeneration is an important cause of vision loss in the United States with over 2 million people affected by the disease. Despite substantial progress in the development of new therapies for wet AMD, the severe visual impairment associated with geographic atrophy in dry AMD or Stargardt disease remains untreatable. Recently, two phase I/II studies involving 18 patients with these diseases have demonstrated that it is possible to safely implant human embryonic stem cell-derived RPE (hESC-RPE) in an attempt to rescue photoreceptors and visual function. The anatomical and functional results are encouraging, with more than half of treated patients experiencing sustained improvements in visual acuity and demonstrating evidence of possible cellular engraftment. However, any conclusions remain tempered by the relatively short follow-up time, lack of a formal control group, poor initial visual acuity, and small number of patients. Aside from an instance of postoperative infectious endophthalmitis, no adverse events related to the cell therapy, such as hyperproliferation, tumorigenicity, or rejection-related inflammation were noted in this initial cohort of 18 patients. These first-in-human safety studies have opened the door to future studies enrolling patients with less advanced disease, treating other diseases that result in RPE loss, employing shorter immunosuppressive regimens, and using alternative strategies for RPE transplantation such as sheets of cells with or without scaffolding to mimic Bruch's membrane. The ultimate goal of these initial safety studies is to promote continued translation of complex biological therapies into meaningful treatment strategies that may address unmet medical needs.