Therapeutic effects of mesenchymal stem cells combined with short hairpin RNA on liver injury induced by hepatitis B virus infection

Liu,Di; Liu,Lin; Wang,Lizheng; Duan,Sizhu; Song,Yanan; Qu,Meng; Gao,Nan; Wu,Jiaxin; Zhang,Haihong; Wu,Hui; Kong,Wei; Yu,Bin; Yu,Xianghui

doi:10.3892/mmr.2017.8096

Therapeutic effects of mesenchymal stem cells combined with short hairpin RNA on liver injury induced by hepatitis B virus infection

Authors:
- Di Liu
- Lin Liu
- Lizheng Wang
- Sizhu Duan
- Yanan Song
- Meng Qu
- Nan Gao
- Jiaxin Wu
- Haihong Zhang
- Hui Wu
- Wei Kong
- Bin Yu
- Xianghui Yu
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Affiliations: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China
Published online on: November 15, 2017 https://doi.org/10.3892/mmr.2017.8096
Pages: 1731-1741
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The clinical symptoms of chronic hepatitis B virus (HBV) infection include severe liver damage, which is associated with the elimination of the HBV‑infected cells by the immune system. It has been suggested that suppression of HBV replication is not sufficient for patients with hepatitis B and the damaged liver function requires restoration. In the present study, mesenchymal stem cells (MSCs) were combined with short hairpin (sh)RNA to treat liver injury and suppress HBV replication in a mouse model. Lx‑shRNA157‑1694 (an shRNA expression plasmid containing two shRNA expression cassettes) and mouse immortal (mi)MSCs stably expressing shRNA (miMSC‑shRNA) were constructed and their suppressive effects on HBV expression were investigated using reverse transcription-polymerase chain reaction (RT‑PCR), ELISA and immunofluorescence. Hepatogenic differentiation of miMSC‑shRNA was induced in vitro and confirmed by morphology, reverse transcription‑semi‑quantitative and ‑quantitative PCR, urea production and Periodic acid‑Schiff staining analyses. miMSCs and the shRNA expression plasmid alone or combined with miMSCs stably expressing shRNA were injected into mice. The former therapeutic regimen successfully suppressed HBV expression in sera and liver tissue, whereas the latter only suppressed HBV expression in liver tissue. Analyses of serum alanine aminotransferase levels, aspartate aminotransferase levels, liver weight/body weight ratio percentage and sirius red staining demonstrated marked amelioration of liver injury in mice treated with both therapeutic regimens. The results of the present study suggest that miMSCs combined with shRNA treatment may alleviate liver injury and suppress HBV expression, thus providing a novel potential therapeutic strategy for the treatment of liver injury induced by HBV infection.

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