Author/Authors :
Yu، Qin نويسنده College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China , , Liu، Lizhen نويسنده Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China , , Lin، Jie نويسنده College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China , , Wang، Yan نويسنده The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China , , Xuan، Xiaobo نويسنده The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China , , Guo، Ying نويسنده College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China , , Hu، Shaojun نويسنده College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China ,
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-1? (SDF-1?) 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-1?/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-1? (HIF-1?) and SDF-1? in the hippocampus
of hypoxic-ischemic rats was detected by Western blotting. To investigate the
role of hypoxia and SDF-1? 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-1? and SDF-
1? 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-1? 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-1?.
Conclusion: This observation illustrates that SDF-1?/CXCR4 axis mediate the migration
of MSCs to a hypoxic-ischemic brain lesion in a rat model.
