Journal Paper

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Journal: یاخته
Year:2015 | Volume: | Issue:
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Title

SDF-1α/CXCR4 AXIS MEDIATES THE MIGRATION OF MESENCHYMAL STEM CELLS TO THE HYPOXIC-ISCHEMIC BRAIN LESION IN A RAT MODEL

Pages

 Start Page 440 | End Page 447

Abstract

 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-1a (SDF-1a) 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-1a/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-1a (HIF-1a) and SDF-1a in the hippocampus of hypoxic-ischemic rats was detected by Western blotting. To investigate the role of hypoxia and SDF-1a 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-1a and SDF- 1a 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-1a 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-1a.Conclusion: This observation illustrates that SDF-1a/CXCR4 axis mediate the MIGRATION of MSCs to a hypoxic-ischemic brain lesion in a rat model.

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