Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration
Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration
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DOI：
10.1038/nbt.4114
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发表时间：
2018-04-01
影响因子：
46.9
通讯作者：
Coffey, Peter J.
中科院分区：
文献类型：
--
作者：
da Cruz, Lyndon;Fynes, Kate;Coffey, Peter J.
黄斑变性（AMD）仍然是失明的主要原因，其中视网膜色素上皮（RPE）的功能障碍和丧失是疾病进展的核心。我们设计了一种RPE贴片，其包含在涂覆的合成基底膜上的完全分化的人胚胎干细胞（hESC）衍生的RPE单层。我们使用专门设计的显微手术工具将贴片植入两名严重渗出性AMD患者的一只眼睛的视网膜下腔。主要终点是不良事件的发生率和严重程度以及最佳矫正视力提高15个字母或以上的受试者比例。我们报告成功交付和生存的视网膜色素上皮补片的生物显微镜和光学相干断层扫描，和视力增益的29和21个字母，分别在两名患者，超过12个月。仅长期使用局部免疫抑制。我们还介绍了临床前手术，细胞安全性和致瘤性研究，导致试验批准。这项工作支持hESC-RPE贴片移植作为AMD再生策略的可行性和安全性。
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.