The Balance Between Immunosuppression Function And Adipogenesis Potential Of Mesenchymal Stem/Stromal Cells

Mesenchymal stem/stromal cells(MSCs),as multipotential adult stem cells,exist in a variety of tissue or organs.MSCs have the ability of self-renewal and directional differentiation,no matter the resource.Obesity,chronic diseases even cancers caused by obesity,have led to increasing attention to the homeostasis of adipose tissue.The increase in the number of adipocytes and cell volume are direct factors in the occurrence of obesity.The increase number of adipocytes mainly come from the differentiation of MSCs and adipogenesis potential of MSCs is closely related to the homeostasis of adipose tissue.In addition to its potential of self-renewal and directional differentiation,MSCs was firstly reported to have immunomodulatory functions in 1998.Up to now,a large number of in vitro experiments and clinical studies have shown that there is interaction between MSCs and immune system.MSCs express a large number of immune mediators after exposing to inflammatory cytokines(e.g.IFNγ/TNFα),which regulate the immune response and then remodel the local inflammatory micro-environment.What we want to explore is whether there is a balance between the immunosuppressive function and differentiation potential of MSCs.We hope to carry out our experiments by exploring one of the differentiation directions of MSCs,named adipogenic differentiation,we are also eager to find out the mechanism of obesity development and the regulation of inflammation on obesity in this processMSCs isolated from human adipose tissue proceed phenotypic and differentiated identification.Then adipogenic differentiation was induced by adipogenesis condition medium with IFNγ/TNFα,lipid droplets were analyzed by Oil Red O staining and Image J software was used to evaluate adipogenesis.Our study revealed that IFNγ/TNFα inhibit the differentiation potential by upregulate SOD2 expression and reduce the ROS level in MSCs.IFNγ/TNFα induced inhibition of adipogenesis was in a manner of SOD2 dependent.Knockdown of SOD2 promoted adipogenesis by enhancing ROS accumulation,but weaken the ability of expressing anti-inflammation mediator in MSCs.Furthermore,non-inflammatory molecule rapamycin can heighten the immunosuppressive function of MSCs while inhibit the potential of adipogenesis The mechanism involved in this balance also showed that relate to ROS levelOur research uncovered that both of IFNy/TNFa and rapamycin promote the immunosuppression function but impair the adipogenesis potential of MSCs SOD2-deficiency MSCs have much stronger adipogenesis potential but weaker ability to express anti-inflammation mediator.We proved that there is a balance between immunosuppressive function and the adipogenesis potential of MSCs from different angles,and we speculated that MSCs may tend to block other functions when they are executing one of their functions,so that they can work better.In other words,there is a mutual exclusion between MSCs’ multiple functions.This study has important biological significance,we will have a more in-depth understanding of the functions of MSCs and this also provide a basic reference for the clinical application of MSCs.