title: SDF-1α/CXCR4 Axis Mediates The Migration of Mesenchymal Stem Cells to The Hypoxic-Ischemic Brain Lesion in A Rat Model.
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-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.
  
  
  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 6×10(6) 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.
  
  
  CONCLUSIONS
  This observation illustrates that SDF-1α/CXCR4 axis mediate the migration of MSCs to a hypoxic-ischemic brain lesion in a rat model.
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China ; Institute of Bioengineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors: Qin
authors: Q
authors: Yu
authors: Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors: Lizhen
authors: L
authors: Liu
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.
authors: Jie
authors: J
authors: Lin
authors: The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors: Yan
authors: Y
authors: Wang
authors: The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
authors: Xiaobo
authors: X
authors: Xuan
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.
authors: Ying
authors: Y
authors: Guo
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.
authors: Shaojun
authors: S
authors: Hu
keywords: CXCR 4; Mesenchymal Stem Cells; Migration; SDF-1α