PDL1 Ig gene-modified BMSCs induce immune tolerance in rat liver trans-plantation / 中国病理生理杂志

ABSTRACT

[ ABSTRACT] AIM: To investigate the effects of bone marrow mesenchymal stem cells ( BMSCs) modified by programed death ligand-1 immunoglobulin ( PDL1 Ig) gene on immune rejection of orthotopic liver transplantation in rats. METHODS:Rat BMSCs were cultured and identified.The protein expression of PDL1 Ig in the BMSCs 72 h after infection with pAdEasy-1/PDL1 Ig was detected by Western blot.Mixed lymphocyte reaction was used to detect the inhibitory effect of BMSCs on the viability of T-lymphocytes in peripheral blood.The male Wistar rats were used as donors (n=40), and the male SD rats were used as recipients ( n=40 ) .The rat model of orthotopic liver transplantation was established by im-proved cuff method for observing acute rejection.The rats were randomly divided into control group, BMSCs treatment group, BMSCs/GFP treatment group and BMSCs/PDL1 Ig treatment group with 10 pairs each.Five rats were executed at the 7th day and the remains were used for measuring the survival time.RESULTS:The expression of PDL1 Ig in the BM-SCs was detected after pAdEasy-1/PDL1 Ig infection.The effect of BMSCs/PDL1 Ig on the viability of the lymphocytes was stronger than that of BMSCs/GFP.The level of IL-4 in BMSCs/PDL1 Ig group was significantly higher than that in the other 3 groups, while the levels of IFN-γand IL-2 were significantly decreased.The liver function in BMSCs/PDL1 Ig group was significantly improved and the levels of ALT, AST and TBil were almost recovered to normal at the 7th day after transplan- tation.Severe rejection reaction was observed in control group, and rejection reactions were decreased with different degrees in BMSCs treatment group and BMSCs/GFP treatment group.Much slighter rejection reaction and significantly longer sur-vival time were showed in BMSCs/PDL1 Ig group than those in the other 3 groups.CONCLUSION:PDL1 Ig-modified BM-SCs inhibit the rejection of liver transplantation in rats and induce the immune tolerance, and the effect is better than that of BMSCs alone.