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

• Published in: Journal of gastroenterology and hepatology 2014-08, Vol.29 (8), p.1620-1628
• Main Authors: Xu, Lanman, Gong, Yuewen, Wang, Benfu, Shi, Keqing, Hou, Yijun, Wang, Liping, Lin, Zuo, Han, Yixiang, Lu, Lu, Chen, Dazhi, Lin, Xiuli, Zeng, Qiqiang, Feng, Wenke, Chen, Yongping
• Format: Article
• Language: English
• Subjects: Adult; Antiviral Agents - therapeutic use; Autografts; bone marrow mesenchymal stem cells; Combined Modality Therapy; Female; Forkhead Transcription Factors; Guanine - analogs & derivatives; Guanine - therapeutic use; Hepatitis B - complications; Hepatitis B virus; Humans; Interleukin-17 - blood; Interleukin-6 - blood; liver cirrhosis; Liver Cirrhosis - etiology; Liver Cirrhosis - immunology; Liver Cirrhosis - therapy; Lymphocyte Count; Male; Mesenchymal Stem Cell Transplantation; Middle Aged; Nuclear Receptor Subfamily 1, Group F, Member 3; Prospective Studies; stem cell transplantation; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Transforming Growth Factor beta - blood; Treg/Th17 cells; Tumor Necrosis Factor-alpha - blood
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/jgh.12653

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 (ABMSCs) 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 Treg/Th17 cells in ABMSCs transplantation in patients with HBV‐LC. Methods In 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 Model for End‐Stage Liver Disease scores, liver function, changes of Treg/Th17 cells, as well as related transcription factors and serum cytokines, were determined. Results Although patients in both groups showed significant improvement after Entecavir treatment, ABMSC transplantation further improved patients' liver function. Moreover, there was a significant increase in Treg cells and a marked decrease in Th17 cells in the transplantation group compared with control, leading to an increased Treg/Th17 ratio. Furthermore, mRNA levels of Treg‐related transcription factor (Foxp3) and Th17‐related transcription factor (RORγt) 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 ABMSCs transplantation was effective in improving liver function in patients with HBV‐LC, which was mediated, at least in part, through the regulation of Treg/Th17 cell balance.