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NDT Advance Access originally published online on November 7, 2007
Nephrology Dialysis Transplantation 2008 23(2):483-491; doi:10.1093/ndt/gfm607
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


Enhanced mobilization of bone marrow cells does not ameliorate renal fibrosis

Geurt Stokman, Jaklien C. Leemans, Ingrid Stroo, Inge Hoedemaeker, Nike Claessen, Gwendoline J. D. Teske, Jan J. Weening and Sandrine Florquin

Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Corresponding to: Geurt Stokman, Academic Medical Center Meibergdreef 9, L2-112, 1105 AZ Amsterdam, The Netherlands. Email: g.stokman{at}amc.uva.nl



  Abstract

Background. The plasticity of bone marrow-derived stem cells, also comprising haematopoietic stem cells, has been shown to extend to renal epithelial lineages. Yet, the low rate of their contribution to the injured kidney has led to questions regarding their significance in tissue repair after acute injury. We describe here the effect of stem cell mobilization therapy on the progression of renal fibrosis in a mouse model of chronic obstructive nephropathy.

Methods. Mice were subjected to unilateral ureter obstruction (UUO) and treated with stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) or saline. Circulating cells were analysed by flow cytometry; labelled bone marrow c-KITHIGH cells were injected into animals subjected to UUO. Granulocytes, macrophages, cellular proliferation or apoptosis and myofibroblasts were detected by immunostaining. Collagen deposition was determined by measuring renal hydroxyproline contents. Cytokine levels were measured by ELISA.

Results. SCF/G-CSF treatment of mice induced significant haematopoietic stem and progenitor cell mobilization from the bone marrow. Although these cells are able to migrate to the obstructed kidney, they did not influence renal damage, fibrosis and inflammatory cell influx.

Conclusions. Although SCF/G-CSF treatment significantly enhanced the availability of haematopoietic stem cells to the obstructed kidney, the progression of renal fibrosis could not be delayed or halted. Our results indicate that effective stem cell mobilization does not alter renal fibrosis.

Keywords: cytokine; fibrosis; kidney; obstructive nephropathy; stem cell; UUO

Received for publication: 25. 6.07
Accepted in revised form: 10. 8.07


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