title: Haematopoietic stem cell migration to the ischemic damaged kidney is not altered by manipulating the SDF-1/CXCR4-axis.
abstract: BACKGROUND
  Haematopoietic stem cells (HSC) have been shown to migrate to the ischemic kidney. The factors that regulate the trafficking of HSC to the ischemic damaged kidney are not fully understood. The stromal cell-derived factor-1 (SDF-1)/CXCR4-axis has been identified as the central signalling axis regulating trafficking of HSC to the bone marrow. Therefore, we hypothesized that SDF-1/CXCR4 interactions are implicated in the migration of HSC to the injured kidney.
  
  
  METHODS
  HSC were isolated from mouse bone marrow and labelled with a cell tracker. Acceptor mice were subjected to unilateral ischemia and received HSC intravenously directly after reperfusion. In addition, in separate groups of acceptor mice, endogenous SDF-1 or HSC-associated CXCR4 was blocked or kidneys were injected with SDF-1.
  
  
  RESULTS
  Exogenous HSC could be detected in the tubules and interstitium of the kidney 24 h after ischemic injury. Importantly, the amount of HSC in the ischemic kidney was markedly higher compared to the contralateral kidney. Neutralizing endogenous SDF-1 or HSC-associated CXCR4 did not prevent the migration of HSC. No increase in the number of labelled HSC could be observed after local administration of SDF-1, as was also determined in bilateral kidney ischemia.
  
  
  CONCLUSIONS
  In conclusion, systemically administered HSC preferentially migrate to the ischemic injured kidney. This migration could not be prevented by blocking the SDF-1/CXCR4-axis or increased after local administration of SDF-1.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. I.Stroo@amc.uva.nl
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stroo
authors.forename: Geurt
authors.initials: G
authors.lastname: Stokman
authors.forename: Gwendoline J D
authors.initials: GJ
authors.lastname: Teske
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans
mesh_terms: D000818:Animals; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007668:Kidney / Q000098:blood supply* / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4