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The chemokine SDF‐1/CXCL12 contributes to the ‘homing’ of umbilical cord blood cells to a hypoxic‐ischemic lesion in the rat brain
Author(s) -
Rosenkranz Katja,
Kumbruch Sandra,
Lebermann Katrin,
Marschner Katrin,
Jensen Arne,
Dermietzel Rolf,
Meier Carola
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22292
Subject(s) - homing (biology) , chemokine , umbilical cord , lesion , neuroscience , medicine , pathology , immunology , biology , inflammation , ecology
Abstract Previous studies have shown that transplanted human umbilical cord blood (hUCB)‐derived mononuclear cells exert therapeutic effects in various animal models of CNS impairments, including those of perinatal hypoxic‐ischemic brain injury. However, the mechanisms of how transplanted cells exert their beneficial effects on the damaged tissue are still unclear. As detection of hUCB cells at the lesion site coincides with the therapeutic effects observed in our model, we investigated the role of the chemokine stromal derived factor (SDF)‐1 (CXCL12) as a possible candidate for chemotaxis‐mediated ‘homing’ of transplanted hUCB cells to a hypoxic‐ischemic lesion in the perinatal rat brain. Following the hypoxic‐ischemic insult expression of SDF‐1 significantly increased in lesioned brain hemispheres and was mainly associated with astrocytes. Transplanted hUCB cells expressing the SDF‐1 receptor CXCR4 migrated to the lesion site within one day. Inhibition of SDF‐1 by application of neutralizing antibodies in vivo resulted in a significantly reduced number of hUCB cells at the lesioned area. The increase in glial SDF‐1 expression shortly after induction of the lesion and hUCB cells expressing the corresponding receptor makes SDF‐1 a potential chemotactic factor for hUCB cell migration. The reduction of hUCB cells present at the lesion site upon functional inhibition of SDF‐1 strengthens the view that the SDF‐1/CXCR4 axis is of major importance for cell ‘homing’. © 2009 Wiley‐Liss, Inc.