ABSTRACT
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 alpha [SDF-1 alpha] 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 alpha /CXCR4 axis in mediating MSC migration in an HIBD model. 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-1 alpha [HIF-1 alpha] and SDF-1 alpha in the hippocampus of hypoxic-ischemic rats was detected by Western blotting. To investigate the role of hypoxia and SDF-1 alpha on migration of MSCs in vitro, MSCs isolated from normal rats were cultured in a hypoxic environment [PO[2]=1%]. Migration of MSCs was detected by the transwell assay. The expression of CXCR4 was tested using Western blotting and flow cytometry. 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 alpha and SDF- 1 alpha 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 alpha 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 alpha . This observation illustrates that SDF-1 alpha /CXCR4 axis mediate the migration of MSCs to a hypoxic-ischemic brain lesion in a rat model
Subject(s)
Animals, Laboratory , Receptors, CXCR4 , Mesenchymal Stem Cells , Hypoxia-Ischemia, Brain , Rats , Models, AnimalABSTRACT
[Objective]To summarize Doctor Xuan Guiqi's experience in the treatment of childhood asthma and the idea of improving the curative efficacy. [Methods]By learning from Doctor Xuan and clearing up medical cases, the author finishes the summary on doctor Xuan's clinical experience on child-hood asthma based on the syndrome differentiation and clinical medication.[Results]The childhood asthma is divided into acute and chronic, the former is divided into cold asthma, heat asthma and wind-phlegm types. At the same time, we strengthen pertinence treatment of clearing heat and removing toxi-city, Qi spasmolytics, dispel ing wind and desensitization, activating blood and eliminating stasis, promoting Qi and regulating middle-jiao and relieving dyspepsia.[Conclusions] Doctor Xuan Guiqi's experience in the diagnosis and treatment of childhood asthma can significantly improve the clinical efficacy , and it is meaningful to clinic.
ABSTRACT
Objective To study the effects ofgranulocyte colony-stimulating factor(G-CSF) and AMD3100 on the proliferation,migration and adhesion of mesenchymal stem cells (MSCs).Methods The proliferation,migration and adhesion of MSCs were detected by MTT chromometry,transwell and adhesion test.Results When the concentration of G-CSF was 200 μg/L and AMD3100 was 0.5 mg/L,the proliferation and migration of MSCs were the strongest.When the concentration of G-CSF was 200 μg/L and AMD3100 was 0 mg/L,the adhesion of MSCs was the strongest.Conclusion The proliferation,migration,adhesion of MSCs are promoted by G-CSF,and inhibited by AMD3100.