Mesenchymal Stem Cells In Immune Regulation Function And Its Mechanism

Mesenchymal stem cells (MSCs) are low-immunogenic cells withimmuno-modulatory capacity, which have bright prospect in treatingimmune-system-related diseases. It is not clear, however, whether MSCs maintainimmuno-modulatory function in pathological environment as they do in normalcondition. Moreover, the mechanism of immuno-modulation by MSCs is still heavilydebated.In part 1, we first investigated that whether the immuno-modulatory capacity is intactin MDS-RA patients bone marrow derived MSCs. The results showed that thecapacity of suppressing T cell proliferation and activation is weakened. Thisphenomenon is correlated with diminished secretion of TGF—β1, 3, FasL from MSCs.We propose that MSCs from pathological environment might be abnormal and shouldnot be used for autologous transplantation.Since fat tissue is a more feasible source for MSCs than bone marrow does, wecompared the immuno-modulatory ability between AMSC and BMSC in part 2. Theresults showed that AMSC and BMSC are similar in suppressing T cell proliferationand activation, and in balancing T helper subpopulation proportion. The difference isthat BMSCs can suppress activated T cell death, while AMSCs cannot.In part 3, we further investigated the mechanism of immuno-modulation by MSCs.We found that MSCs express Nanog, and through Nanog expression, indirectlyregulate secretion of TGF—βand Dkk—1. Secretion of TGF—βand Dkk—1 accountpartly for immuno-modulatory function of MSCs.In part 4, we investigated in mice model the duration of immuno-modulatory effectafter MSC infusion, and its relation with infused MSC dose. The results showed thatthe immuno-modulatory effect is dose-dependant in vivo, and that this effect is most prominent with 2 weeks, begins to diminish in 1 month, and vanishes in 2 month.