The chemokine SDF-1/CXCL12 contributes to the 'homing' of umbilical cord blood cells to a hypoxic-ischemic lesion in the rat brain.
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'.
Rosenkranz
Katja
K
Department of Neuroanatomy and Mol. Brain Research, Ruhr-University, Bochum, Germany.
Kumbruch
Sandra
S
Lebermann
Katrin
K
Marschner
Katrin
K
Jensen
Arne
A
Dermietzel
Rolf
R
Meier
Carola
C
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D054426:Chemokine CXCL2 / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear / Q000502:physiology* / Q000637:transplantation; D009457:Neuroglia / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000378:metabolism; D013997:Time Factors
D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4