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

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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.