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

使用细胞表面抗原分离人感光前体细胞用于视网膜干细胞治疗

• 批准号: MR/M015688/1
• 负责人: Jane Sowden
• 金额: $ 105.21万
• 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: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM015688%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. New three-dimensional retinal culture methods can produce large numbers of new retinal cells. Our hypothesis is that photoreceptor cells generated from these 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 human cells to transplant into the diseased retina. We will develop live cell sorting methods using antibodies that bind to special markers on the surface of the immature photoreceptor cells providing a tag to isolate them with. The efficacy of isolated cells for retinal repair will be tested in transplantation experiments in animal models of retinal disease. This study will develop cell isolation protocols for human photoreceptor precursor cells, which is a requisite 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。新的三维视网膜培养方法可以产生大量新的视网膜细胞。我们的假设是，从这些干细胞培养物中产生的感光细胞对于人类治疗将是有效和安全的，只要它们被处理，使得它们在细胞培养皿中达到正确的阶段，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人类细胞以移植到患病视网膜中的方法。我们将开发活细胞分选方法，使用抗体与未成熟感光细胞表面的特殊标记物结合，提供标签来分离它们。分离细胞用于视网膜修复的功效将在视网膜疾病动物模型的移植实验中进行测试。这项研究将开发人类感光细胞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必要步骤。

项目成果

Transplantation of Photoreceptor Precursors Isolated via a Cell Surface Biomarker Panel From Embryonic Stem Cell-Derived Self-Forming Retina.

• DOI: 10.1002/stem.2051
• 发表时间: 2015-08
• 期刊: Stem cells (Dayton, Ohio)
• 作者: Lakowski J;Gonzalez-Cordero A;West EL;Han YT;Welby E;Naeem A;Blackford SJ;Bainbridge JW;Pearson RA;Ali RR;Sowden JC
• 通讯作者: Sowden JC

Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.

• DOI: 10.1016/j.stemcr.2017.07.022
• 发表时间: 2017-09-12
• 期刊: Stem cell reports
• 影响因子: 5.9
• 作者: Gonzalez-Cordero A;Kruczek K;Naeem A;Fernando M;Kloc M;Ribeiro J;Goh D;Duran Y;Blackford SJI;Abelleira-Hervas L;Sampson RD;Shum IO;Branch MJ;Gardner PJ;Sowden JC;Bainbridge JWB;Smith AJ;West EL;Pearson RA;Ali RR
• 通讯作者: Ali RR

Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration.

• DOI: 10.1016/j.stemcr.2017.04.030
• 发表时间: 2017-06-06
• 期刊: Stem cell reports
• 影响因子: 5.9
• 作者: Kruczek K;Gonzalez-Cordero A;Goh D;Naeem A;Jonikas M;Blackford SJI;Kloc M;Duran Y;Georgiadis A;Sampson RD;Maswood RN;Smith AJ;Decembrini S;Arsenijevic Y;Sowden JC;Pearson RA;West EL;Ali RR
• 通讯作者: Ali RR

Towards retinal cell replacement therapy: isolation of human stem-cell- derived photoreceptors using cell surface biomarkers

走向视网膜细胞替代疗法：使用细胞表面生物标志物分离人类干细胞衍生的光感受器

• 发表时间: 2017
• 作者: Lakowski J