Abstract 185: Additional Benefit of Cyclosporine-Assisted Adipose-Derived Mesenchymal Stem Cell Therapy for Against Acute Kidney Ischemia-Reperfusion Injury

Abstract

Objectives: This study tested the hypothesis that cyclsporine (CsA)-supported adipose-derived mesenchymal stem cell (ADMSC) therapy offered superior attenuation of acute ischemia-reperfusion (IR) kidney injury than either therapy alone. Methods: Adult SD-rats (n=40) were equally divided into group 1 (sham controls), group 2 (IR injury), group 3 [IR + CsA (20 mg/kg at 1 and 24 hr after procedure)], group 4 [ADMSC (1.2x106) at 1, 6 and 24 h after procedure], and group 5 (IR + CsA-ADMSC). Results: By 72 h after IR procedure, creatinine level and the ratio of urine protein to creatinine were highest in group 2 and lowest in group 1, significantly higher in groups 3 and 4 than in group 5, but they showed no differences between groups 3 and 4 (all p<0.0001). The inflammatory biomarkers at mRNA (MMP-9, RANTES, TNF-α), protein (TNF-α, NF-κB, ICAM-1, PDGF), and cellular (CD68+) levels of IR kidney showed an identical pattern to creatinine level in all groups (all p<0.0001). The protein expressions of oxidative stress (oxidized protein), ROS (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP) and DNA damage markers (γH2AX+, PNCA+ cells) exhibited a similar pattern to inflammatory mediators (all p<0.0001) amongst all groups (all p<0.0001). Anti-oxidant biomarkers at cellular (GPx, GR, HO-1) and protein (NQO-1, HO-1, eNOS) levels, and endothelial progenitor cell markers (CXCR4+, SDF-1α+) were lowest in groups 1 and 2, higher in groups 3 and 4 and highest in group 5 (all p<0.0001). Conclusions: Combination therapy using cyclosporine-plus-ADMSCs offers improved protection against acute IR kidney injury. Key words: cyclosporine, adipose-derived mesenchymal stem cell, acute kidney ischemia-reperfusion injury, combination therapy, inflammation, oxidative stress, apoptosis