The Effect of Isogeneic Mesenchymal Stem Cells Reinfused on Prolong Rat Cardiac Allograft Survive with Immune Tolerance
|Keywords||isogeneic mesenchymal stem cells acute rejection hearttransplantation immune regulation|
[Objective]: To explore the immune regulation effect and mechanism of isogeneicbone marrow mesenchymal stem cells in heterotopic rat heart transplantation.[Methods]: Wistar rats (donor) heart allografts were transplanted into the cervix ofF344rats (receptor). Eighty F344rats were divided into four groups (20rats in eachgroup). In group A，untreated；In group B, recipients received2xl06/lml MSCs givenat the one day before and the first day, the second day after heart transplantation viatail vein；In group C，recipients received CsA10mg/kg from day0to day10throughintraperitoneal injection；In Group D, recipients received2xl06/lml MSCs given at theone day before and the first day, the second day after heart transplantation via tail veinand CsA1mg/kg from day0to day10through intraperitoneal injection. Observedonor heart survival time by touch and the situation of5rats in each group afteroperation. On the seventh day after transplantation，the5rats in each group weresacrificed and the spleen were taken out for observing the diversities of the number ofthe expression of the Foxp3by real-time PCR; allograft heart’s tissues were made intoparaffin-embedded specimens to detect rat heart histological change and grade(ISHLT).5recipients in each group were sacrificed on day5、7and10respectively，serum levels of IL-2、IL-4、IL-10and IFN-γ were tested by ELISA.[Results]:Compare with group A, the survival time of donor heart in the group B、C、D was significantly prolong(P<0.05), and it was longer in group D than that in othergroups(P<0.05)；Compared with group A，the expression of the Foxp3mRNA waslower than group B、C and D(P<0.05), there was higher changes in group D than thatin other groups(P<0.05)；Group A ISHLT score was significantly higher than groupB、C and D(P<0.05)，and there was lesser Pathological changes in group D than thatin other groups；The level of IL-2and IFN-γ in group A were higher than group B、Cand D(P<0.05), there was lower changes in group D than that in other groups (P<0.05);The level of IL-4and IL-10in group A were lower than group B、C and Dat the same time(P<0.05), there was higher changes in group D than that in othergroups(P<0.05);.There was no significant difference between group B and groupC(P>0.05) in above mentioned.[Conclusion]: Intravenous administration of bone marrow derived MSCs alleviateimmunorejection in heterotopic rat heart transplantation. The mechanisms involve thesuppressive effect of MSCs on the expression of the Foxp3mRNA and modulation oncytokine.