Open Access

Biological effects of bone marrow mesenchymal stem cells on hepatitis B virus in vitro

  • Authors:
    • Wei‑Ping Zheng
    • Bo‑Ya Zhang
    • Zhong‑Yang Shen
    • Ming‑Li Yin
    • Yi Cao
    • Hong‑Li Song
  • View Affiliations

  • Published online on: March 15, 2017     https://doi.org/10.3892/mmr.2017.6330
  • Pages: 2551-2559
  • Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the effects of co‑culturing bone marrow‑derived mesenchymal stem cells (BM-MSCs) cultured with hepatitis B virus (HBV)‑infected lymphocytes in vitro. BM‑MSCs and lymphocytes from Brown Norway rats were obtained from the bone marrow and spleen, respectively. Rats were divided into the following five experimental groups: Group 1, splenic lymphocytes (SLCs); group 2, HepG2.2.15 cells; group 3, BM‑MSCs + HepG2.2.15 cells; group 4, SLCs + HepG2.2.15 cells; and group 5, SLCs + BM‑MSCs + HepG2.2.15 cells. The viability of lymphocytes and HepG2.2.15 cells was assessed using the MTT assay at 24, 48 and 72 h, respectively. Levels of supernatant HBV DNA and intracellular HBV covalently closed circular DNA (cccDNA) were measured using quantitative polymerase chain reaction. Supernatant cytokine levels were measured by enzyme‑linked immunosorbent assay (ELISA). T cell subsets were quantified by flow cytometry using fluorescence‑labeled antibodies. In addition, the HBV genome sequence was analyzed by direct gene sequencing. Levels of HBV DNA and cccDNA in group 5 were lower when compared with those in group 3 or group 4, with a significant difference observed at 48 h. The secretion of interferon‑γ was negatively correlated with the level of HBV DNA, whereas secretion of interleukin (IL)‑10 and IL‑22 were positively correlated with the level of HBV DNA. Flow cytometry demonstrated that the percentage of CD3+CD8+ T cells was positively correlated with the levels of HBV DNA, and the CD3+CD4+/CD3+CD8+ ratio was negatively correlated with the level of HBV DNA. Almost no mutations in the HBV DNA sequence were detected in HepG2.2.15 cells co‑cultured with BM‑MSCs, SLCs, or in the two types of cells combined. BM‑MSCs inhibited the expression of HBV DNA and enhanced the clearance of HBV, which may have been mediated by the regulation of the Tc1/Tc2 cell balance and the mode of cytokine secretion to modulate cytokine expression.
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May-2017
Volume 15 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Zheng WP, Zhang BY, Shen ZY, Yin ML, Cao Y and Song HL: Biological effects of bone marrow mesenchymal stem cells on hepatitis B virus in vitro. Mol Med Rep 15: 2551-2559, 2017
APA
Zheng, W., Zhang, B., Shen, Z., Yin, M., Cao, Y., & Song, H. (2017). Biological effects of bone marrow mesenchymal stem cells on hepatitis B virus in vitro. Molecular Medicine Reports, 15, 2551-2559. https://doi.org/10.3892/mmr.2017.6330
MLA
Zheng, W., Zhang, B., Shen, Z., Yin, M., Cao, Y., Song, H."Biological effects of bone marrow mesenchymal stem cells on hepatitis B virus in vitro". Molecular Medicine Reports 15.5 (2017): 2551-2559.
Chicago
Zheng, W., Zhang, B., Shen, Z., Yin, M., Cao, Y., Song, H."Biological effects of bone marrow mesenchymal stem cells on hepatitis B virus in vitro". Molecular Medicine Reports 15, no. 5 (2017): 2551-2559. https://doi.org/10.3892/mmr.2017.6330