sdf-1α/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 functional recovery of the brain after hypoxic-ischemic brain damage (hibd). however, the mechanism regulating msc migration to a hypoxic-ischemic lesion is poorly understood. interaction between stromal cell-derived factor-1α (sdf-1α) and its cognate receptor cxc chemokine receptor 4 (cxcr4) is crucial for homing and migration of multiple stem cell types. in this study, we investigate the potential role of sdf-1α/cxcr4 axis in mediating msc migration in an hibd model. materials and methods: in this experimental study, we first established the animal model of hibd using the neonatal rat. bone marrow mscs were cultured and labeled with 5-bromo-21-deoxyuridine (brdu) after which 6×106 cells were intravenously injected into the rat. brdu positive mscs in the hippocampus were detected by immunohistochemical analyses. the expression of hypoxia-inducible factor-1α (hif-1α) and sdf-1α in the hippocampus of hypoxic-ischemic rats was detected by western blotting. to investigate the role of hypoxia and sdf-1α on migration of mscs in vitro, mscs isolated from normal rats were cultured in a hypoxic environment (po2=1%). migration of mscs was detected by the transwell assay. the expression of cxcr4 was tested using western blotting and flow cytometry. results: brdu-labeled mscs were found in the rat brain, which suggested that transplanted mscs migrated to the site of the hypoxic-ischemic brain tissue. hif-1α and sdf- 1α significantly increased in the hippocampal formations of hibd rats in a time-dependent manner. they peaked on day 7 and were stably expressed until day 21. migration of mscs in vitro was promoted by sdf-1α under hypoxia and inhibited by the cxcr4 inhibitor amd3100. the expression of cxcr4 on mscs was elevated by hypoxia stimulation as well as microdosage treatment of sdf-1α. conclusion: this observation illustrates that sdf-1α/cxcr4 axis mediate the migration of mscs to a hypoxic-ischemic brain lesion in a rat model.