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

肾缺血-再灌注损伤是由于长期的血压下降（如严重感染或外伤）导致的肾缺血后血流恢复所致。肾脏被白细胞如巨噬细胞浸润，许多肾细胞死亡，导致急性肾功能衰竭，需要透析。与年轻人相比，老年人更容易患上急性肾衰竭，这是其他疾病的并发症，结果也更糟。该方案将利用最先进的胚胎干细胞技术，结合遗传和药理学操作，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脏功能。巨噬细胞治疗的效果将在老年小鼠中进行专门研究，这些小鼠在肾脏血流量减少一段时间后出现比年轻小鼠更严重的肾功能衰竭。这项工作将为进一步研究利用胚胎干细胞衍生的潜在抗炎和修复特性奠定基础。巨噬细胞。

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.