Development of a cellular therapy for dry Age Related Macular Degeneration (AMD) using retinal pigment epithelium (RPE) derived from human embryonic stem cells (hESC)

使用源自人类胚胎干细胞 (hESC) 的视网膜色素上皮 (RPE) 开发治疗干性年龄相关性黄斑变性 (AMD) 的细胞疗法

• 批准号: 207258553
• 负责人: Privatdozent Dr. Michael Koss
• 金额: --
• 依托单位: Roski Eye Institute
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/207258553?language=en
• 关键词: Development; cellular; therapy; dry; Age

Dry age related macular degeneration (AMD) is a degenerative disease of the retina, which leads to a progressive decrease in central visual acuity. In countries like the Federal Republic of Germany or the United States of America it is the main reason of blindness for the over 65 aged with approximately 12 million patients. It is caused by the cell death of the retinal pigment epithelium (RPE), which is integral for maintenance of healthy photoreceptors (PR) and together with the PR provides the transducing interface for visual perception. We hypothesize that lost RPE can be restored in an animal disease model through transplantation with human embryonic stem cells (hESC). Stem cells are premature and primitve cells, that have a big advantage in the underlying research project. They bear a high replication rate through cell division, which is supported by the fact that there is the relative paucity of cell numbers needed for each patient (1.5x105 RPE) which means that it is easily achievable with working and master cell banks. Additionally each cell has the potential to develop to a mature RPE cell. Preliminary results demostrate that hESC have disease-modyfing activity of of hESC-RPE in animal models of retinal dystrophy. In cooperation with the CalTech university it is planned to monitor blood flow dynamics in the choriocapillaris that supports the RPE and to measure changes in the photoreceptor pigment. Both are essential physiologic processes to evaluate the feasibility of hESC transplanted RPE.

干性年龄相关性黄斑变性（AMD）是一种视网膜退行性疾病，其导致中心视力进行性下降。在像联邦共和国德国或美国这样的国家，它是65岁以上老年人失明的主要原因，大约有1200万患者。它是由视网膜色素上皮（RPE）的细胞死亡引起的，视网膜色素上皮（RPE）是维持健康光感受器（PR）的组成部分，并且与PR一起提供视觉感知的转导界面。我们假设通过移植人胚胎干细胞（hESC）可以在动物疾病模型中恢复丢失的RPE。干细胞是未成熟的原始细胞，在基础研究项目中具有很大的优势。它们通过细胞分裂具有高复制率，这得到了以下事实的支持：每个患者所需的细胞数量相对较少（1.5x105 RPE），这意味着使用工作和主细胞库很容易实现。此外，每个细胞都有可能发育成成熟的RPE细胞。初步结果证实hESC对视网膜营养不良动物模型具有hESC-RPE的疾病修饰活性。与加州理工大学合作，计划监测支持RPE的脉络膜毛细血管中的血流动力学，并测量感光色素的变化。这两个过程都是评估hESC移植RPE可行性的重要生理过程。

项目成果

In vivo detection of hESC-RPE cells via confocal near-infrared fundus reflectance.

通过共焦近红外眼底反射对 hESC-RPE 细胞进行体内检测

• DOI: 10.3928/23258160-20130715-09
• 发表时间: 2013
• 期刊: Ophthalmic surgery, lasers & imaging retina
• 作者: Ribeiro R;Oregon A;Diniz B;Fernandes RB;Koss MJ;Charafeddin W;Thomas P;Tomas BB;Maia M;Chader G;Hinton DR;Humayun MS
• 通讯作者: Humayun MS