Immunological effect induced by mesenchymal stem cells in a rat liver transplantation model.

Abstract

The aim of the present study was to investigate the immunological effect induced by bone marrow mesenchymal stem cells (MSCs) in rats that had undergone an orthotopic liver transplantation (OLT). MSCs were isolated and cultured from the bone marrow tissue of Lewis rats. In total, 42 rat OLT models were established and equally distributed into three groups. Group A received an OLT only, group B were also intramuscularly injected with tacrolimus (FK506), while group C were not only administered FK506, but also received MSCs. On day 7 post-surgery, the blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were measured. In addition, pathological changes were observed in the liver, levels of immune cytokines, including transforming growth factor (TGF)-α1, interleukin (IL)-10 and IL-12, were determined using immunohistochemistry, MSC homing was assessed and the survival times of the patients were recorded. Liver function, as assessed by the levels of ALT, AST and TBIL, was shown to improve in group C when compared with groups B and A (both P<0.01). In addition, survival analysis revealed that the survival times in groups B (median, 44 days) and C (median, 63 days) were significantly longer compared with group A (median, 11 days; both P<0.01). The survival rate of group C was also higher compared with group B (P<0.01). Pathological examination demonstrated strong acute rejection in group A, a mild acute rejection in group B and the mildest reaction in group C. In addition, immunohistochemistry revealed that TGF-α1 and IL-10 expression was stronger in groups C and B, with group C exhibiting more significant expression than group B. By contrast, expression levels of IL-12 in groups A, B and C were positive, weak-positive and negative, respectively. Therefore, postoperative immunosuppression induced by MSCs is important for the alleviation of immune rejection from recipient-to-graft, and may induce immune tolerance in rat OLT models.