CELL THERAPY FOR THE VASODEGENERATIVE STAGES OF DIABETIC RETINOPATHY

糖尿病视网膜病变血管变性阶段的细胞疗法

• 批准号: G0801962/1
• 负责人: Alan Stitt
• 金额: $ 63.7万
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801962%2F1
• 关键词: CELL; THERAPY; VASODEGENERATIVE; STAGES; DIABETIC

Diabetic Retinopathy is a leading cause of visual impairment. Even with current management regimens it continues to significantly reduce the quality of life for millions of affected individuals. Late stages of diabetic retinopathy can be treated or contained to some extent by pan-retinal laser photocoagulation but at the expense of causing damage to large areas of functional retina. Although a range of other therapeutic approaches are being developed, most are directed to end-stage retinopathy and fail to address the early pathology characterised by microvascular cell dysfunction and death. New treatments focusing on these early changes such as cell therapies to repair/replace abnormal diabetic vasculature are needed. This study will establish the baselines for the development of a novel ?stem cell? therapy based on induction of therapeutic angiogenesis by introducing highly defined populations of bone marrow-derived endothelial progenitor cells (EPCs) into the ischemic retina. Although EPCs have been shown to promote effective revascularisation of ischemic hearts in animal models, their definitive role in the ischemic retina remains unclear. This study will thoroughly assess any benefit obtained from injecting distinct EPCs into the vitreous of ischemic retinas.Recently, it has been suggested that EPCs from type 1 diabetic patients are dysfunctional and display a reduced capacity to promote vascular repair. We plan to fully evaluate the function of EPC populations isolated from diabetic mice, and will test, for the first time, the possibility of healing diabetic dysfunctional progenitors by treating them with a statin.EPCs are a highly heterogeneous group of cells. Depending on the subpopulation that is injected into the ischemic retina we anticipate promoting vascular repair by transplanting progenitors that become endothelial cells. Other EPC subpopulation transplants could actually exacerbate retinal damage by becoming inflammatory cells and this response this is important to determine. This study will clearly define the cell type with the capacity to promote vascular recovery and, importantly, will evaluate retinal function after cell therapy.It is expected that endothelial progenitors from diabetic mice will be dysfunctional. We anticipate obtaining these cells from marrow, expanding them in the laboratory, correcting any inherent defect using statin treatment prior to ?transplanting? them into donor eyes. We expect that this approach will address the progressive retinal vascular damage that happens in diabetes and, ultimately, prevent vision loss.

糖尿病视网膜病变是导致视力损害的主要原因。即使采用目前的管理方案，它仍在显著降低数百万受影响者的生活质量。晚期糖尿病视网膜病变可以通过全视网膜激光光凝治疗或在一定程度上控制，但代价是对大面积的功能性视网膜造成损伤。虽然正在开发一系列其他治疗方法，但大多数都针对终末期视网膜病变，未能解决以微血管细胞功能障碍和死亡为特征的早期病理学。需要针对这些早期变化的新治疗方法，例如修复/替换异常糖尿病血管系统的细胞疗法。这项研究将建立一个新的发展基线？干细胞？基于通过将高度确定的骨髓来源的内皮祖细胞（EPCs）群体引入缺血视网膜来诱导治疗性血管生成的疗法。 尽管EPCs在动物模型中已被证明可促进缺血心脏的有效血管重建，但其在缺血性视网膜中的确切作用仍不清楚。这项研究将彻底评估从注射不同的EPCs到缺血性retinas.Recently的玻璃体中获得的任何好处，有人建议，EPCs从1型糖尿病患者是功能失调，并显示能力降低，以促进血管修复。我们计划全面评估从糖尿病小鼠中分离的EPC群体的功能，并将首次测试用他汀类药物治疗糖尿病功能障碍祖细胞的可能性。EPC是一组高度异质性的细胞。根据注射到缺血性视网膜中的亚群，我们预期通过移植成为内皮细胞的祖细胞来促进血管修复。其他EPC亚群移植实际上可能通过成为炎性细胞而加剧视网膜损伤，这种反应很重要。这项研究将清楚地确定具有促进血管恢复能力的细胞类型，重要的是，将评估细胞治疗后的视网膜功能。我们期望从骨髓中获得这些细胞，在实验室中扩增它们，在治疗前使用他汀类药物治疗纠正任何固有缺陷。移植？捐赠者的眼睛。我们希望这种方法能够解决糖尿病中发生的渐进性视网膜血管损伤，并最终防止视力丧失。