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

Lanman Xu; Yuewen Gong; Benfu Wang; Keqing Shi; Yijun Hou; Liping Wang; Zuo Lin; Yixiang Han; Lu Lu; Dazhi Chen; Xiuli Lin; Qiqiang Zeng; Wenke Feng; Yongping Chen

doi:10.1111/jgh.12653

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

J Gastroenterol Hepatol. 2014 Aug;29(8):1620-8. doi: 10.1111/jgh.12653.

Authors

Lanman Xu¹, Yuewen Gong, Benfu Wang, Keqing Shi, Yijun Hou, Liping Wang, Zuo Lin, Yixiang Han, Lu Lu, Dazhi Chen, Xiuli Lin, Qiqiang Zeng, Wenke Feng, Yongping Chen

Affiliation

¹ Department of Infection and Liver Diseases of the First Affiliated Hospital and Liver Research Center, Wenzhou Medical University, Wenzhou, Zhejiang, China.

PMID: 24942592
DOI: 10.1111/jgh.12653

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 (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.

Keywords: Treg/Th17 cells; bone marrow mesenchymal stem cells; hepatitis B virus; liver cirrhosis; stem cell transplantation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antiviral Agents / therapeutic use
Autografts
Combined Modality Therapy
Female
Forkhead Transcription Factors
Guanine / analogs & derivatives
Guanine / therapeutic use
Hepatitis B / complications*
Humans
Interleukin-17 / blood
Interleukin-6 / blood
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
T-Lymphocytes, Regulatory / immunology*
Th17 Cells / immunology*
Transforming Growth Factor beta / blood
Tumor Necrosis Factor-alpha / blood

Substances

Antiviral Agents
FOXP3 protein, human
Forkhead Transcription Factors
Interleukin-17
Interleukin-6
Nuclear Receptor Subfamily 1, Group F, Member 3
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha
entecavir
Guanine