Effects of angiopoietin-2 on endothelial progenitor cells in acute murine ischemic kidney injury

The purpose of this study was to evaluate, whether Angiopoetin-2 (Ang-2) can increase the nephroprotective potential of early endothelial outgrowth cells (eEOCs) in acute murine ischemic kidney injury (AKI). Previously published results showed renoprotective effects of eEOCs in AKI. Ang-2 on the other hand is critically involved in mediating angiogenesis. Therefore, syngeneic murine eEOCs were pretreated with Ang-2. The cells were incubated for 1 hour with a concentration of 400 ng/ml or 800 ng/ml of Ang-2. In all experiments, male 8-12 week-old C57Bl/6N mice were subjected to a renal ischemia of 40 minutes by occluding the left kidney. The solutions of the different experimental groups had to be injected into the vessel of the contralateral, right kidney after these 40 minutes and the removal of the occlusion of the left kidney. Finally, the right kidney was removed. These steps had to be done within 2 minutes and ensured, that the renal function was now done only by the pre-suffered left kidney. The renal function and its morphology were analyzed after 48 hours. The results showed that Ang-2 modulates eEOCs in AKI in a dose-dependent way. While an Ang-2 concentration of 400 ng/ml significantly stimulated the cells´ effectiveness in AKI, doubelling the concentration (800 ng/ml) dramatically aggravated postischemic renal dysfunction. The study points towards potential dangers of cell-based therapies of AKI.2014-06-0