摘要目的 在发现IFN-γ可通过JAK/STAT途径上调人胎盘源间充质干细胞(human placenta-derived mesenchymal stromal cells,hPMSCs)程序性死亡蛋白配体2(programed death ligand 2,PDL2)表达的基础上,研究IFN-γ、PDL2及JAK/STAT信号通路对hPMSCs黏附、增殖和迁移功能的实时调节作用.方法 应用酶消化法分离hPMSCs.实时细胞分析仪(real-time cell analysis,RTCA)分别动态分析IFN-γ、阻断型PDL2单克隆抗体(McAb)和JAK抑制剂干预下hPMSCs黏附、增殖及迁移的变化特点.结果 IFN-γ在40~80 h之间明显抑制hPMSCs的增殖,抑制hPMSCs的非靶向迁移,但对hPMSCs的黏附无明显调节作用.抗体阻断实验结果显示,PDL2阻断抗体促进了hPMSCs的黏附,抑制了hPMSCs的非靶向迁移,但对hPMSCs的增殖无明显的调节作用.IFN-γ和阻断型PDL2 McAb共同作用下hPMSCs的增殖与单独阻断型PDL2 McAb处理组相比,hPMSCs的增殖能力明显下降.JAK抑制剂可显著抑制hPMSCs的黏附、迁移和增殖.结论 IFN-γ可明显抑制hPMSCs的迁移和增殖;PDL2可上调hPMSCs的迁移能力,下调其黏附能力;hPMSCs的黏附、迁移及增殖受JAK/STAT途径控制.

abstractsObjective To investigate the real-time regulatory effects of IFN-γ, programed death ligand 2(PDL2) and janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway on the adherence, proliferation and migration of human placenta-derived mesenchymal stem cells(hPMSCs) based on a finding that IFN-γ could enhance the expression of PDL2 in hPMSCs through JAK/STAT signaling pathway.Methods hPMSCs were isolated by using enzyme digestion method and then co-cultured with IFN-γ, anti-PDL2 monoclonal antibody (anti-PDL2 McAb) and JAK inhibitor, respectively.Real-time cell analysis (RTCA) was used to detect the dynamic changes in the adherence, proliferation and migration of hPMSCs following various interventions.Results IFN-γ remarkably suppressed hPMSCs proliferation during the period from 40 hours to 80 hours after intervention and also inhibited the non-targeted migration of hPMSCs.However, hPMSCs adherence was not affected by IFN-γ.Co-culturing hPMSCs with anti-PDL2 McAb significantly enhanced hPMSCs adhesion and inhibited their non-targeted migration, but had no significant effect on hPMSCs proliferation.Furthermore, the proliferation of hPMSCs co-cultured with IFN-γ and anti-PDL2 McAb was significantly inhibited as compared with that of anti-PDL2McAb treatment group.The adhesion, migration and proliferation of hPMSCs were significantly inhibited after co-culturing them with JAK inhibitor.Conclusion IFN-γ can remarkably suppress the proliferation and migration of hPMSCs.PDL2 can enhance the migration and inhibit the adhesion of hPMSCs.JAK/STAT signaling pathway is involved in regulating the adhesion, migration and proliferation of hPMSCs.