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

肾缺血-再灌注损伤是指由于严重感染或创伤等原因引起的血压长期降低后，血流恢复到供血不足的肾脏。肾脏被巨噬细胞等白细胞渗透，许多肾细胞死亡，导致急性肾功能衰竭，需要进行透析。与年轻人相比，老年人更容易患上急性肾功能衰竭，成为其他疾病的并发症，结果也更差。这项提议将使用最先进的胚胎干细胞技术以及遗传和药物操作来产生大量表达抗炎酶血红素加氧酶-1的巨噬细胞。这些胚胎干细胞来源的巨噬细胞的性质将在细胞培养中得到仔细观察，然后它们将作为细胞治疗的药物应用于缺血再灌注损伤的小鼠。据预测，它们将显著保护肾功能。巨噬细胞疗法的效果将在肾血流减少一段时间后出现比青年鼠更严重的肾功能衰竭的老年鼠身上进行专门检测。这项工作将为进一步研究胚胎干细胞来源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.