年龄相关性黄斑变性(Age-related macular degeneration, AMD)是造成失明的主要原因之一，其疾病进展的核心在于，随着年龄的不断增长，视网膜色素上皮(retinal pigment epithelium, RPE)逐渐出现功能障碍和丢失。日前，一项发表于《Nature biotechnology》杂志的研究中，研究者利用人胚胎干细胞(human embryonic stem cell, hESC)设计了一种RPE补片，对干细胞用于治疗AMD进行了初步探索。
研究者设计的RPE补片由完全分化的hESC形成的RPE单层膜组成，覆盖在合成的基底膜上。使用一种专门设计的显微手术工具，研究者将hESC-RPE补片植入 AMD患者的一只眼的视网膜下空间。共有两名患者接受此项手术。手术前研究者对hESC-RPE进行了成瘤性研究，通过免疫染色和流式细胞学检测hESC-RPE是否含有有分化潜能的多能干细胞，并将不同浓度（最高50%）的hESC注入RPE，观察其是否能够存活并分化。两项检测均得到阴性结果，即hESC-RPE并未显示出明显成瘤性。而hESC单独注入小鼠模型中，可观察到明显的成瘤。
两名患者术前均诊断为急性重度渗出型AMD。主要研究终点为不良事件的发生率和严重程度，以及最佳矫正视力的提高。共出现三项严重不良事件，均判定为与RPE不相关。在12个月的时间里，两名患者的视力分别提高了29和21个字母（检测方法：Early Treatment Diabetic Retinopathy Study，一种通过辨认字母的个数判定视力的方法）。
这项1期临床试验表明，hESC-RPE补片移植可以作为AMD的一种治疗方法，显示出其初步的可行性和安全性。
Abstract
Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD.
本文为原创翻译，特此声明！Reference: Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat Biotechnol. 2018 Apr;36(4):328-337.
来源： 大医编