Jagged-2 enhances immunomodulatory activity in adipose derived mesenchymal stem cells

Adipose derived Mesenchymal stem cells (AMSCs) are able to expand in vitro and undergo differentiation into multiple cell lineages, yet have low immunogenicity while exhibiting several immunoregulatory characteristics. We sought to investigate the immunomodulatory mechanisms of AMSCs to better understand their immunogenic properties. Following 10 days of chondrogenic differentiation or 48 hours of IFN-gamma pretreatment, AMSCs retained low level immunogenicity but prominent immunoregulatory activity and AMSC immunogenicity was enhanced by chondrogenic differentiation or IFN-gamma treatment. We found Jagged-2 expression was significantly elevated following chondrogenic differentiation or IFN-gamma pretreatment. Jagged-2-RNA interference experiments suggested that Jagged-2-siRNA2 suppresses Jagged-2 expression during chondrogenic differentiation and in IFN-gamma pretreated AMSCs. Besides, Jagged-2 interference attenuated immunosuppressive activity by mixed lymphocyte culture and mitogen stimulation experiments. So, the immunoregulatory activity of AMSCs, to some extent dependent upon Jagged-2, might be stronger after multilineage differentiation or influence from inflammatory factors. This may also be why rejection does not occur after allogeneic AMSCs differentiate into committed cells.