Using cell surface antigens for the isolation of photoreceptor precursor cells for retinal stem cell therapy

使用细胞表面抗原分离感光前体细胞用于视网膜干细胞治疗

• 批准号: G0901550/1
• 负责人: Jane Sowden
• 金额: $ 68.43万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901550%2F1
• 关键词: Using; cell; surface; antigens; isolation

Diseases of the retina resulting in the death of the light-sensing photoreceptor cells are the leading cause of blindness in the developed world. These conditions affect 1 in 3000 people from birth and more than 10% of the ageing population. They are currently untreatable and irreversible. We recently demonstrated in proof-of-concept experiments in mice that replacing lost photoreceptors by cell transplantation is a feasible clinical treatment strategy. We discovered that by transplanting immature photoreceptor cells, these cells can make new functional photoreceptors in the diseased retina, and restore some visual function. To translate our findings to a human therapy we need to isolate equivalent human photoreceptor precursors from stem cell cultures grown in the laboratory. Our hypothesis is that retinal cells generated from stem cell cultures will be effective and safe for human therapy provided they are treated so that they reach exactly the right stage in a cell culture dish and provided only these correctly-staged cells are transplanted. One critical challenge therefore is developing methods to identify and collect correctly-staged donor cells to transplant into the diseased retina. We will develop methods for isolating live cells by using antibodies that bind to special markers on the surface of the immature photoreceptor cells. The efficiency of the newly isolated cells for retinal repair will be tested in transplantation experiments. This research will develop cell isolation protocols for human photoreceptor precursor cells, which is an essential step towards development of clinical trials for incurable retinal diseases causing blindness.

在发达国家，导致感光细胞死亡的视网膜疾病是导致失明的主要原因。这些疾病影响到1/3000的出生人口和10%以上的老龄人口。它们目前是无法治疗和不可逆转的。我们最近在小鼠的概念验证实验中证明，通过细胞移植替代丢失的光感受器是一种可行的临床治疗策略。我们发现，通过移植未成熟的感光细胞，这些细胞可以在患病的视网膜中产生新的功能性感光细胞，并恢复一些视觉功能。为了将我们的发现转化为人类疗法，我们需要从实验室培养的干细胞中分离出等同的人类感光细胞前体。我们的假设是，从干细胞培养物产生的视网膜细胞将是有效和安全的人类治疗，只要它们被处理，使它们在细胞培养皿中达到完全正确的阶段，并且只移植这些正确阶段的细胞。因此，一个关键的挑战是开发识别和收集正确分期的供体细胞以移植到患病视网膜中的方法。我们将开发通过使用与未成熟感光细胞表面的特殊标记结合的抗体分离活细胞的方法。新分离的细胞用于视网膜修复的效率将在移植实验中进行测试。这项研究将开发人类感光前体细胞的细胞分离方案，这是对导致失明的无法治愈的视网膜疾病进行临床试验的重要一步。