Adipose-derived mesenchymal stem cell-supported ciprofloxacin therapy effectively protects the kidney parenchyma and functional integrity against acute pyelonephritis damage in rodents.

This study revealed that adipose-derived mesenchymal stem cell-facilitated ciprofloxacin therapy effectively protected the kidney parenchyma and functional integrity against acute pyelonephritis damage in rodents. In vitro studies revealed that adipose-derived mesenchymal stem cell-derived media significantly suppressed the number of bacterial colony formation units (P < 0.0001). Additionally, the combination of adipose-derived mesenchymal stem cell-ciprofloxacin was superior to either treatment alone on suppressing lipopolysaccharide-induced inflammatory reactions in macrophages and peripheral blood-derived mononuclear cells and attenuated lipopolysaccharide-induced apoptosis/DNA damage in uroepithelial cells (Simian virus Hydrologic Unit Code 1) (all P < 0.0001). Sprague-Dawley rats were categorized into groups 1 (sham-control)/2 (acute pyelonephritis)/3 (acute pyelonephritis-ciprofloxacin)/4 (acute pyelonephritis- adipose-derived mesenchymal stem cell)/5 (acute pyelonephritis-adipose-derived mesenchymal stem cell-ciprofloxacin), and kidneys were harvested by day 5 after acute pyelonephritis induction. The in vivo results revealed that the day-5 mortality rate and creatinine levels at days 2 and 5 were significantly greater in group 2 than in groups 1 and 5 (P = 0.01), whereas the kidney injury score and inflammatory cell infiltration in the kidney were highest in group 2, lowest in group 1, and significantly greater in groups 3 and 4 than in group 5; however, there was no difference between groups 3 and 4 (all P < 0.0001). The upstream inflammatory signaling (toll-like receptor-4, myeloid differentiation primary response 88, tumor necrosis factor receptor associated factor 6 and nuclear factor-kappa B) and downstream inflammatory signaling (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) biomarkers exhibited identical patterns of kidney injury scores among the groups (all P < 0.0001). The results of the present study showed that adipose-derived mesenchymal stem cell-facilitated ciprofloxacin reduced inflammatory signaling-induced kidney parenchymal damage and acute pyelonephritis-induced mortality and preserved kidney function.