"Transplant human PBMC to establish a ""human-mouse""xenogeneic graft-versus-host disease model" / 中国免疫学杂志

Objective:To explore the suitable mouse strains,and establish stable human-miceX-GVHD model.Methods:This study selected the Nude Mice and NOD/SCID, and gave them sublethal dose of γ-ray irradiation whole body , and then intraperitoneal transplanted human peripheral blood mononuclear cells ( PBMC) to establish xenogeneic acute graft-versus-host disease model.By detection of human T cells in the mice′s tail venous blood,tissues,organs of the infiltration and other indicators (By flow cy-tometry and immunohistochemistry ) ,we compared the human immune cell infiltration rates in the two mouse model and recorded the survival time.Finally,we determined the appropriate strains of mice to establish X-GVHD.Optimization means were transfer ways and the appropriate amount of human PBMC ,and the best time to observe the changes of T cell phenotype and function.Results:The NOD/SCID mouse was more suitable for inducing human-mouseX-GVHD model,and there were no significant differences between intrap-eritoneal injection and intravenous injection.Transfer human PBMC more than 5 ×107 can establish human-mouseX-GVHD model.Using the optimized experimental conditions to establish the human-mouseX-GVHD model,we found the 7-11 days was the best time to observe the changes of T cell phenotype and function ,and the average survival time was(14.16±1.77)days.Conclusion:Human-miceX-GVHD model can be successfully established by intraperitoneal injection of 5×107 human PBMC into NOD/SCID, and the best time to observe the changes of T cell phenotype and function is between 7-11 days.

MicroRNA-21 is involved in osteosarcoma cell invasion and migration.

MicroRNAs are involved in different cancer-related processes. MicroRNA-21 (miR-21), as an oncomiR, is overexpressed in all kinds of tumors and the role of miR-21 in carcinogenesis is elucidated in many cancers gradually. However, the function of miR-21 in osteosarcoma is still unclear. In our study, we found that miR-21 was significantly overexpressed in osteosarcoma tissues. More importantly, we confirmed that knockdown of miR-21 greatly decreased cell invasion and migration of MG-63. Furthermore, we identified that RECK (reversion-inducing-cysteine-rich protein with kazal motifs), a tumor suppressor gene, was a direct target of miR-21. Finally, the expression of RECK protein negatively correlated with the expression of miR-21 in human osteosarcoma tissues, indicating the potential regulation of RECK by miR-21. Our results suggest that miR-21 expression has a key role in regulating cellular processes in osteosarcoma, likely through regulating RECK and may serve as a therapeutic target.