Abstract 14845: Targeted Delivery of Endothelial Cells Overexpressing Interleukin-8 Receptors Attenuates Ischemia-Reperfusion Acute Kidney Injury
Introduction: Ischemia-reperfusion acute kidney injury (AKI) damages the renal microvascular endothelium, prolonging the underperfused state of the kidney and exacerbating renal injury. Injured kidney tissue expresses large amounts of the neutrophil chemoattractant interleukin-8 (IL8) which binds to receptors (IL8RA and IL8RB) on neutrophil membranes.
Hypothesis: This study tested the hypothesis that systemic transfusion of rat aortic endothelial cells (ECs) transduced with IL8 receptors (IL8RA/RB-ECs) ameliorates renal dysfunction and promotes structural recovery of the kidney following ischemia-reperfusion AKI.
Methods and Results: Male Sprague-Dawley rats were subjected to AKI by clamping the left renal artery for 45 min and removing the right kidney. At time of reperfusion, 1.5x106 IL8RA/RB-ECs or vehicle were infused in the femoral vein. At 24 hrs after AKI, serum creatinine increased ~ 7-8 fold in the vehicle treated group and then gradually decreased towards baseline (Fig). In rats that received IL8RA/RB-ECs, the rise in serum creatinine was significantly blunted (46% lower at 24 hrs and 69% lower at 72 hrs). At 6 wks after AKI, the left kidney was harvested and stained with picrosirius red for assessment of collagen area (index of fibrosis) and CD31 (capillary
density). Kidneys from rats that received IL8RA/RB-ECs showed significantly less fibrosis (2.1±0.3% vs. 8.0±2.6%) and higher capillary density (18.0±2.3 vs. 8.5±0.9, p<0.05 for both) compared to kidneys from vehicle-treated rats.
Conclusions: Using an innovative strategy of targeted delivery of ECs equipped with a homing device (IL8 receptors), ECs mimic the behavior of neutrophils and are attracted to the site of injury in order to accelerate tissue repair and preserve renal function following ischemia-reperfusion AKI. This novel approach of targeted systemic delivery of cell-based therapy for treatment of AKI is an attractive model that lends itself to future applications in humans.
Author Disclosures: F.G. Hage: None. D. Xing: None. Y. Guo: None. S. Oparil: None. Y. Chen: None. P.W. Sanders: None.
- © 2014 by American Heart Association, Inc.