Randomized trial of autologous bone marrow mesenchymal stem cells transplantation for hepatitis B virus cirrhosis: Regulation of Treg/Th17 cells

Abstract Background and Aim Liver cirrhosis is one of the major consequences of hepatitis B virus ( HBV ) infection, and transplantation of autologous bone marrow mesenchymal stem cells ( ABMSC s) is one of promising therapies for patients with HBV ‐related liver cirrhosis ( HBV ‐ LC ). However, the mechanism is unclear. The aim of the current study was to explore the role of T reg/ T h17 cells in ABMSC s transplantation in patients with HBV ‐ LC . Methods I n this prospective study, 56 patients were enrolled and randomly assigned to transplantation group and control group. After 24‐week follow‐up, 39 patients completed the study (20 cases in transplantation group and 19 cases in control group). The M odel for E nd‐ S tage L iver D isease scores, liver function, changes of T reg/ T h17 cells, as well as related transcription factors and serum cytokines, were determined. Results Although patients in both groups showed significant improvement after E ntecavir treatment, ABMSC transplantation further improved patients' liver function. Moreover, there was a significant increase in T reg cells and a marked decrease in T h17 cells in the transplantation group compared with control, leading to an increased T reg/ T h17 ratio. Furthermore, m RNA levels of T reg‐related transcription factor ( F oxp3) and T h17‐related transcription factor ( ROR γt) were increased and decreased, respectively. In addition, serum transforming growth factor‐β levels were significantly higher at early weeks of transplantation, while serum levels of interleukin‐17, tumor necrosis factor‐α, and interleukin‐6 were significantly lower in patients in the transplantation group compared with control. Conclusion ABMSC s transplantation was effective in improving liver function in patients with HBV ‐ LC , which was mediated, at least in part, through the regulation of T reg/ T h17 cell balance.