ABSTRACT
Background@#Orthotopic liver transplantation is the only option for patients with end-stage liver disease and hepatocellular carcinoma. Post-transplant immunosuppressive therapy is important to prevent graft failure. We investigated the effectiveness of tacrolimus (FK506) and their mechanisms for liver transplant immune tolerance in an outbred rat LT model. @*Results@#To investigate the therapeutic effect of the FK506 on outbred rat LT model, FK506 and postoperative therapy were administered subcutaneously once or twice daily to transplanted rats. Histopathological and immunohistochemical analyses were conducted for all groups. The regulation of inflammatory cytokine signaling in the spleen was analyzed by flow cytometry. FK506 attenuated allograft rejection and increased survival in rat orthotopic liver transplantation models. The FK506-treated group had reduced serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Furthermore, FK506 decreased the expression of inflammatory cytokines and the activation of pathogenic Th1 and Th17 cells in the liver. @*Conclusions@#Taken together, we revealed that FK506 ameliorated strong allograft rejection in outbred liver transplantation model by anti-inflammatory effect and inhibitory peroperty of pathogenic T cells.
ABSTRACT
Human embryonic stem cell (hESC) culture system has been changing culture conditions from conventional to xeno-free for therapeutic cell applications, and N-glycolylneuraminic acid (Neu5Gc) could be a useful indicator of xenogeneic contaminations in hESCs because human cells can no longer produce it genetically. We set up the humanized culture condition using commercially available humanized materials and two different adaptation methods: sequential or direct. SNUhES4 and H1 hESC lines, previously established in conventional culture conditions, were maintained using the humanized culture condition and were examined for the presence of Neu5Gc. The hESCs showed the same morphology and character as those of the conventional culture condition. Moreover, they were negative for Neu5Gc within two passages without loss of pluripotency. This study suggested that this method can effectively cleanse previously established hESC lines, bringing them one step closer to being clinical-grade hESCs.
Subject(s)
Humans , Human Embryonic Stem Cells , MethodsABSTRACT
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a unique protein, participating in inflammation, immune response, and cell growth. Previous reports showed that MIF-polymorphisms are associated with an increased risk for various inflammatory diseases. OBJECTIVE: This study was designed to investigate the effect of MIF polymorphisms on Behcet's disease (BD). METHODS: A total of 362 patients with BD and 290 healthy controls were genotyped. We also performed RT-PCR analysis, ELISA, and immunohistochemical stain for MIF. RESULTS: We could not find statistically significant differences in the genotype frequencies of the MIF-794[CATT]5-8 repeat polymorphism or MIF-173 G>C polymorphism between BD patients and controls. Immunohistochemical analysis showed that MIF protein was diffusely distributed throughout epidermis and subcutaneous fat tissue from the skin lesions of patients with BD and erythema nodosum. CONCLUSION: Contrary to earlier reports, serum MIF levels were decreased in patients with BD, and the prescence of polymorphisms in the MIF promoter region was not associated with disease susceptibility. Nevertheless, MIF may play a role in cutaneous inflammation in BD.