The Combination of G-CSF/AMD3100 Mobilizes Bone Marrow-Derived Stem Cells to Rescue Mice from Cisplatin-Induced Acute Kidney Injury

Background: Several studies have confirmed that mobilizing bone marrow-derived stem cells (BMSCs) ameliorates renal function loss following cisplatin-induced acute kidney injury (AKI). The aim of this study was to explore whether the combination of G-CSF/AMD3100 exerts beneficial effects with respect to renal function recovery in a mouse model of cisplatin-induced nephrotoxicity. Methods: : C57BL/6J mice received intraperitoneal injections of G-CSF (200 μg/kg/d) for 5 consecutive days. On the day of the last injection, the mice received a single subcutaneous dose of AMD3100 (5 mg/kg) 1 hour before cisplatin 20 mg/kg injection. 96 hours after cisplatin injection, the mice were euthanized, blood and tissue samples were collected to assess renal function and tissue damage. Cell mobilization was assessed by flow cytometry. Results: : Mice pretreated with G-CSF/AMD3100 exhibited longer survival and significantly lower serum creatinine and BUN levels than mice treated with only G-CSF or saline, exhibited attenuated tissue injury and cell death and enhanced tissue repair and cell regeneration. C57BL/6J mice pretreated with G-CSF/AMD3100 exhibited higher numbers of stem cells in peripheral blood than mice treated with only G-CSF or saline. Furthermore, G-CSF/AMD3100 administration prevented increases in the expression of proinflammatory factors, such as IL-6 and TNF-α, and increased the expression of the anti-inflammatory factor IL-10. Conclusions: : These results suggest that G-CSF/AMD3100 mobilizes bone marrow cells to improve renal function and prevent cisplatin-induced renal tubular injury and that the combination of G-CSF/AMD3100 is superior to G-CSF alone for preventing AKI. This combination may represent a new therapeutic option for the treatment of AKI and warrants further investigation.