SDF-1α/CXCR4 Axis Mediates The Migration Of Mesenchymal Stem Cells To The Hypoxic-Ischemic Brain Lesion In A Rat Model
Journal Title: Cell Journal(Yakhteh) - Year 2015, Vol 16, Issue 4
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. 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.
Authors and Affiliations
Qin Yu, Lizhen Liu, Jie Lin, Yan Wang, Xiaobo Xuan, Ying Guo, Shaojun Hu
Keywords
Related Articles
- EP ID EP594014
- DOI 10.22074/cellj.2015.504
- Views 148
- Downloads 0
Protective Effects of Diallyl Sulfide and Curcumin Separately against Thallium-Induced Toxicity in Rats
Thallium acetate (TI) is a cumulative poison intimately accompanied by an increase in reactive oxygen species (ROS) formation that represents an important risk factor for tissue injury and malfunction. This study aims to...
Total Antioxidant Capacity And Lipid Peroxidation In Semen Of Patient With Hyperviscosity
Semen hyperviscosity (SHV) is one of the factors involved in deficiency in sperm function. This research aimed to evaluate seminal plasma total antioxidant capacity (TAC) and malondialdehyde (MDA) levels in infertile pat...
Identification Of Reliable Reference Genes For Quantification Of MicroRNAs In Serum Samples Of Sulfur Mustard-Exposed Veterans
Objective In spite of accumulating information about pathological aspects of sulfur mustard (SM), the precise mechanism responsible for its effects is not well understood. Circulating microRNAs (miRNAs) are promising bio...
Optimization of Buffalo (Bubalus bubalis) Embryonic Stem Cell Culture System
Objective: In order to retain an undifferentiated pluripotent state, embryonic stem (ES) cells have to be cultured on feeder cell layers. However, use of feeder layers limits stem cell research, since experimental data m...
In Vitro Toxic Effects Of Zinc Oxide Nanoparticles On Rat Adipose Tissue-Derived Mesenchymal Stem Cells
Objective Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, bio- sensors, food additives, pigments, manufacture of rubber products, and electronic materi- als. There are several studies about the ef...