title: 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-α1and 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.
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China ; Research Laboratory of Disease Genomics, Cancer Research Institute, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Digestive and Vascular Surgery Center, First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830054, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Digestive and Vascular Surgery Center, First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830054, P.R. China ; Xinjiang Organ Transplant Research Institute, First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830054, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China.
authors.forename: Haijiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Oncology Center, First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830054, P.R. China.
authors.forename: Weizheng
authors.initials: W
authors.lastname: Ji
authors.affiliation: Stem Cell Laboratory of Medical Research Center, First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830054, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
keywords: animal model; immune effect; mesenchymal stem cells; orthotopic liver transplantation