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

在发达国家，视网膜疾病导致感光细胞死亡是导致失明的主要原因。这些疾病从出生起就影响每3000人中就有一人受到影响，超过10%的老龄人口受到影响。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，通过细胞移植来取代丢失的光感受器是一种可行的临床治疗策略。我们发现，通过移植未成熟的光感受器细胞，这些细胞可以在病变的视网膜中产生新的功能性光感受器，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量的人类光感受器前体。我们的假设是，从干细胞培养中产生的视网膜细胞对于人类治疗将是有效和安全的，只要它们得到治疗，使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方法来识别和收集分期正确的供体细胞，以便移植到患病的视网膜中。我们将开发分离活细胞的方法，方法是使用与未成熟光感受器细胞表面的特殊标记结合的抗体。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光感受器前体细胞的细胞分离方案，这是开发导致失明的不可治愈的视网膜疾病临床试验的关键一步。

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.