Protective effect of combined therapy with hyperbaric oxygen and autologous adipose-derived mesenchymal stem cells on renal function in rodent after acute ischemia-reperfusion injury

Background: This study tested the hypothesis that combined hyperbaric oxygen (HBO) and autologous adipose-derived mesenchymal stem cell (ADMSC) therapy was superior to either alone at protecting renal function in rodents after acute ischemia-reperfusion (IR) injury. Methods and results: Adult-male SD rats (n = 40) were equally categorized: group 1 (sham-operated control); group 2 (IR + 50 μg medium intra-renal artery administration); group 3 [IR + HBO (at 1.5 h and days 1 and 2 after IR)]; group 4 [IR + ADMSC (2.0×10⁶cells/5.0×10⁵/per each renal artery and 1×10⁶by intravenous injection at 1.5 h after IR]; and group 5 (IR + HBO-ADMSC). By 72 hr after IR, the circulating levels of BUN/creatinine and ratio of urine protein/creatinine were significantly highest in group 2, lowest in group 1, significantly increased in group 5 than in groups 3 and 4, but not different between latter two groups, whereas the circulating levels of EPCs and soluble-angiogenesis biomarkers (SDF-1α/HIF-1α) exhibited an opposite pattern to BUN/creatinine among the five groups (all P<0.001). The kidney injury score, ROS (fluorescent intensity of H2DCFDA dye in kidney), inflammation (F4/80+, CD14+ cells) and glomerular-tubular injury score (WT-1/KIM-1) displayed an identical pattern whereas the integrity of podocyte components exhibited an opposite pattern to BUN/creatinine among the five groups (all P<0.0001). The protein expressions of inflammatory (MMP-9/TNF-α/NF-kB/ICAM-1), oxidative-stress (NOX-1/NOx-2/oxidized protein) and apoptotic (mitochondrial-Bax/cleaved-caspase3/PARP) markers showed an identical pattern to BUN/creatinine (all P<0.001). Conclusion: Combined ADMSC-HBO therapy was superior to either one alone at protecting the kidney from acute IR injury.