ISCHAEMIC ACUTE RENAL FAILURE AND AGE: MODULATION BY ANTI-INFLAMMATORY EMBRYONIC STEM CELL-DERIVED MACROPHAGES

缺血性急性肾衰竭和年龄：抗炎胚胎干细胞源性巨噬细胞的调节

• 批准号: G0801235/1
• 负责人: Jeremy Hughes
• 金额: $ 57.33万
• 依托单位: University of Edinburgh
• 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=G0801235%2F1
• 关键词: ISCHAEMIC; ACUTE; RENAL; FAILURE; AGE

Renal ischaemia-reperfusion injury follows the restoration of blood flow to kidneys starved of blood following a prolonged lowering of blood pressure caused, for example, by severe infection or trauma. The kidney is infiltrated with white blood cells such as macrophages and many kidney cells die resulting in acute renal failure and the requirement for dialysis. Elderly individuals are more vulnerable to developing acute renal failure as a complication of other illnesses and have a worse outcome compared to younger individuals. This proposal will use state-of-the-art embryonic stem cell technology together with genetic and pharmacological manipulation to generate significant numbers of macrophages that express the anti-inflammatory enzyme hemeoxygenase-1. The nature of these embryonic stem cell-derived macrophages will be scrutinised in cell culture and they will then be administered to mice with ischaemia-reperfusion injury as ?cell therapy? with the prediction that they will significantly protect kidney function. The effect of macrophage cell therapy will be specifically examined in old mice that develop worse renal failure than young mice following a period of diminished blood flow to the kidney. This work will lay the foundation for further studies utilising the potential anti-inflammatory and reparative properties of embryonic stem cell-derived ?designer? macrophages.

肾缺血-再灌注损伤是在例如由严重感染或创伤引起的血压长期降低后，血流恢复到缺乏血液的肾脏。肾脏被白色血细胞如巨噬细胞浸润，许多肾细胞死亡，导致急性肾衰竭和需要透析。老年人更容易发生急性肾衰竭作为其他疾病的并发症，并且与年轻人相比结局更差。该提案将使用最先进的胚胎干细胞技术以及遗传和药理学操作来产生大量表达抗炎酶血红素加氧酶-1的巨噬细胞。这些胚胎干细胞衍生的巨噬细胞的性质将在细胞培养中进行仔细检查，然后将它们用于缺血再灌注损伤的小鼠。细胞疗法预测它们将显著保护肾功能。巨噬细胞治疗的效果将在老年小鼠中进行具体检查，老年小鼠在肾脏血流减少一段时间后发生比年轻小鼠更严重的肾衰竭。这项工作将奠定基础，进一步研究利用潜在的抗炎和修复特性的胚胎干细胞衍生的？设计师？巨噬细胞