Enhanced mobilization of bone marrow cells does not ameliorate renal fibrosis.
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-KIT(HIGH) 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.
Stokman
Geurt
G
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. g.stokman@amc.uva.nl
Leemans
Jaklien C
JC
Stroo
Ingrid
I
Hoedemaeker
Inge
I
Claessen
Nike
N
Teske
Gwendoline J D
GJ
Weening
Jan J
JJ
Florquin
Sandrine
S
D000818:Animals; D001854:Bone Marrow Cells; D018450:Disease Progression; D005355:Fibrosis; D019650:Hematopoietic Stem Cell Mobilization; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL