SDF-1?/CXCR4 Axis Mediates the Migration of Mesenchymal Stem Cells to the Hypoxic-Ischemic Brain Lesion in A Rat Model

Objective: transplantation of mesenchymal stem cells (mscs) can promote functionalrecovery of the brain after hypoxic-ischemic brain damage (hibd). however, the mechanismregulating msc migration to a hypoxic-ischemic lesion is poorly understood. interactionbetween stromal cell-derived factor-1? (sdf-1?) and its cognate receptor cxcchemokine receptor 4 (cxcr4) is crucial for homing and migration of multiple stem celltypes. in this study, we investigate the potential role of sdf-1?/cxcr4 axis in mediatingmsc migration in an hibd model.materials and methods: in this experimental study, we first established the animal modelof hibd using the neonatal rat. bone marrow mscs were cultured and labeled with5-bromo-21-deoxyuridine (brdu) after which 6×106 cells were intravenously injected intothe rat. brdu positive mscs in the hippocampus were detected by immunohistochemicalanalyses. the expression of hypoxia-inducible factor-1? (hif-1?) and sdf-1? in the hippocampusof hypoxic-ischemic rats was detected by western blotting. to investigate therole of hypoxia and sdf-1? on migration of mscs in vitro, mscs isolated from normalrats were cultured in a hypoxic environment (po2=1%). migration of mscs was detectedby the transwell assay. the expression of cxcr4 was tested using western blotting andflow cytometry.results: brdu-labeled mscs were found in the rat brain, which suggested that transplantedmscs migrated to the site of the hypoxic-ischemic brain tissue. hif-1? and sdf-1? significantly increased in the hippocampal formations of hibd rats in a time-dependentmanner. they peaked on day 7 and were stably expressed until day 21. migration of mscsin vitro was promoted by sdf-1? under hypoxia and inhibited by the cxcr4 inhibitoramd3100. the expression of cxcr4 on mscs was elevated by hypoxia stimulation aswell as microdosage treatment of sdf-1?.conclusion: this observation illustrates that sdf-1?/cxcr4 axis mediate the migrationof mscs to a hypoxic-ischemic brain lesion in a rat model.