Tohoku J. Exp. Med., 2007, 213(4)

Bone Marrow-Derived Cells Mobilized by Granulocyte-Colony Stimulating Factor Facilitate Vascular Regeneration in Mouse Kidney after Ischemia/Reperfusion Injury

SUSUMU AKIHAMA,¹ KAZUNARI SATO,² SHIGERU SATOH,¹ NORIHIKO TSUCHIYA,¹ TETSURO KATO,³ ATSUSHI KOMATSUDA,⁴ MAKOTO HIROKAWA,⁴ KENICHI SAWADA,⁴ HIROSHI NANJO⁵ and TOMONORI HABUCHI¹

¹Department of Urology, Akita University School of Medicine, Akita, Japan
²Hiraka General Hospital, Yokote, Japan
³Akita Prefectural Health Care Center, Akita, Japan
⁴Department of Internal Medicine, Akita University School of Medicine, Akita, Japan
⁵Department of Pathology, Akita University School of Medicine, Akita, Japan

Bone marrow-derived cells (BMDC) play crucial roles in tissue regeneration. Granulocyte-colony stimulating factor (G-CSF) mobilizes BMDC and may facilitate the repair of kidney tissues after ischemia/reperfusion (I/R) injury. The tissue protective action of resveratrol, an antioxidant, might modify the regenerating potential of BMDC in I/R renal injury. This study examined whether G-CSF and/or resveratrol affect the recruitment of BMDC into vascular endothelial cells and renal tubular cells and the kidney function after I/R injury. I/R renal injury was induced in female mice that had been lethally irradiated and transplanted with male bone marrow cells. The mice were given saline, resveratrol or G-CSF, daily for 7 days. Non-irradiated and non-bone-marrow-transplanted female mice, which underwent the same kidney injury, were included as control. White blood cell (WBC) count and serum creatinine were monitored. Immunohistologic evaluation for renal tubular cells (cytokeratin) and endothelial cells (factor VIII-related antigen), and fluorescence in situ hybridization for mouse Y chromosome were performed. Although WBC was significantly higher in the G-CSF group, there was no significant difference in creatinine levels among all groups. Factor VIII-related antigen-positive cells with a Y-chromosome signal were identified in the capillary wall between renal tubuli and most frequently seen in the G-CSF group (p < 0.0001). Resveratrol did not affect kidney recovery in this model. No cytokeratin-positive renal tubular cells having a Y-chromosome signal were identified. In conclusion, BMDC are recruited into endothelial cell in I/R renal injury without apparent renal tubular cell regeneration, and G-CSF facilitates the endothelial cell regeneration.

keywords —— Granulocyte-colony stimulating factor; resveratrol; bone-marrow-derived cell; regeneration; ischemia/reperfusion injury

© 2007 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2007, 213, 341-349

Correspondence: Prof. Tomonori Habuchi, Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.

e-mail: thabuchi@doc.med.akita-u.ac.jp