Effect of allogeneic bone marrow–derived mesenchymal stem cells transplantation in a polyI:C-induced primary biliary cirrhosis mouse model

Abstract

Primary biliary cirrhosis (PBC) is a slowly progressive autoimmune disease of unknown mechanism. We established a PBC animal model by injecting C57BL/6 mice with polyinosinic-polycytidylic acid sodium (polyI:C) to investigate the therapeutic effect of bone marrow-derived mesenchymal stem cells (BM-MSC) on this model. After 6 weeks of MSC infusion, serum aminotransferase and autoimmune antibodies declined, and histological examination by hematoxylin and eosin staining showed significant amelioration of monocytes infiltration around bile ducts of mice treated with BM-MSC. Interestingly, allogeneic BM-MSC transplantation markedly increased CD4(+)Foxp3(+) regulatory T cells in peripheral blood as well as in lymph nodes when analyzed by flow cytometry. Further examination showed serum TGF-β1 increased but IFN-γ decreased significantly in PBC mice treated with MSC, while with no obvious change in IL-10 expression. Our results for the first time suggested that BM-MSC transplantation could regulate systemic immune response and enhance recovery in liver inflammation of PBC mice, raising the possibility for clinical application of allogeneic MSC in treatment of early-stage PBC patients.

Comparative proteomics study on liver mitochondria of primary biliary cirrhosis mouse model

“…We collected liver samples at the end of four, eight, and 12 weeks, because during these time points the mice would be in the early stage of PBC [11-13]. Histopathological analysis was performed to evaluate the progress of the disease (Figure 1).…”

“…Mouse model was constructed according to the method described previously [11,13] with minor modification. Adult 6–8 week-old C57BL/6 female mice were injected intraperitoneally twice a week with poly I:C (Sigma-Aldrich, St. Louis, USA) (PBC model group) at a dose of 5 mg/kg body weight or with the same volume of saline water (control group).…”

Novel Treatment Strategies for Primary Biliary Cholangitis

“…It has been reported as a treatment in other diseases with an autoimmune pathogenesis such as lupus erythematosus, immune thrombocytopenia, and rheumatoid arthritis. [111][112][113] The rationale for this novel therapeutic line is based on the immunomodulatory properties of the MSCs, including the ability to suppress the proliferation of T lymphocytes and change the cytokine secretion profile of dendritic cells, T-helper lymphocytes, and natural killer cells, resulting in a more anti-inflammatory phenotype and increasing the proportion of regulatory T lymphocytes. Accordingly, two recent clinical studies including a few patients with PBC and an incomplete response to UDCA were infused with umbilical cord-derived MSCs or allogenic bone marrow mesenchymal stromal/stem cells.…”

Mesenchymal stem cells enhance autophagy of human intrahepatic biliary epithelial cells in vitro

“…Mesenchymal stem cells (MSCs) are known to enhance the autophagy of cells against apoptosis . As a effective treatment to PBC, MSC transplantations applied to patients have been reported .…”

“…[4][5][6] As a effective treatment to PBC, MSC transplantations applied to patients have been reported. [7][8][9] A significant increase in signal transducer and activator of transcription 3 (STAT3) levels was observed in the IBECs of patients with PBC relative to normal ones. 10 In the previous study, the abnormal autophagy was observed in IBECs of PBC model mice, in which MSC treatment alleviates histopathological small bile duct injury and induces autophagy in above cells; also, STAT3 was regulated by MSCs.…”