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Mobilization of Bone Marrow Cells by G-CSF Rescues Mice from Cisplatin-Induced Renal Failure, and M-CSF Enhances the Effects of G-CSF

Masayoshi Iwasaki^*,, Yasushi Adachi^*,, Keizo Minamino^*, Yasuhiro Suzuki^*, Yuming Zhang^*, Mitsuhiko Okigaki, Keiji Nakano^*, Yasushi Koike^*, Jianfeng Wang^*, Hiromi Mukaide^*, Shigeru Taketani^||, Yasukiyo Mori, Hakuo Takahashi, Toshiji Iwasaka^, and Susumu Ikehara^*,

^* First Department of Pathology, Second Department of Internal Medicine, Regeneration Research Center for Intractable Diseases, and Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, Moriguchi, Osaka; and ^|| Department of Biotechnology, Kyoto Institute of Technology, Sakyo-ku, Kyoto, Japan

Address correspondence to: Dr. Susumu Ikehara, First Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan, 570-8506. Phone: 81-6-6993-9429; Fax: 81-6-6994-8283; E-mail: ikehara{at}takii.kmu.ac.jp

Cisplatin, which is a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury. This article examines whether G-CSF and/or M-CSF rescues mice from renal failure induced by cisplatin. BALB/c mice received intraperitoneal injections with or without G-CSF and/or M-CSF for 5 d (from day –5 to day –1). The day after the last injection of G-CSF and/or M-CSF (day 0), the mice received an intraperitoneal injection of cisplatin. When pretreated with G-CSF or G-CSF + M-CSF, the mice showed longer survival and lower serum creatinine and blood urea nitrogen levels than mice that had been received injections of M-CSF or saline. Histologically, pretreatment with G-CSF or G-CSF + M-CSF attenuated the damage to renal tubules induced by cisplatin. BALB/c mice that had received a transplant of bone marrow cells of enhanced green fluorescent protein (EGFP)-transgenic mice ([EGFPBALB/c] mice) were treated with or without G-CSF and/or M-CSF, followed by injection of cisplatin as well as above. [EGFPBALB/c] mice that were treated with G-CSF or G-CSF + M-CSF showed a significantly higher number of EGFP⁺ tubular epithelial cells in the kidney than mice that were treated with only M-CSF or saline. These results suggest that bone marrow cells mobilized by G-CSF accelerate the improvement in renal functions and prevent the renal tubular injury induced by cisplatin and that M-CSF enhances the effects of G-CSF.

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