Therapeutic effects of mesenchymal stem cells combined with short hairpin RNA on liver injury induced by hepatitis B virus infection.
Therapeutic effects of mesenchymal stem cells combined with short hairpin RNA on liver injury induced by hepatitis B virus infection.
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间充质干细胞联合短发夹RNA对乙型肝炎病毒感染所致肝损伤的治疗作用
DOI：
10.3892/mmr.2017.8096
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发表时间：
2018-01
影响因子：
3.4
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Liu D;Liu L;Wang L;Duan S;Song Y;Qu M;Gao N;Wu J;Zhang H;Wu H;Kong W;Yu B;Yu X
慢性乙型肝炎病毒（HBV）感染的临床症状包括严重的肝损伤，这与免疫系统清除 HBV 感染细胞有关。有研究认为，对乙型肝炎患者来说，抑制 HBV 复制是不够的，受损的肝功能需要恢复。在本研究中，间充质干细胞（MSCs）与短发夹（sh）RNA相结合，在小鼠模型中治疗肝损伤并抑制 HBV 复制。研究人员构建了Lx-shRNA157-1694（一种含有两个shRNA表达盒的shRNA表达质粒）和稳定表达shRNA的小鼠永生（mi）间充质干细胞（miMSC-shRNA），并使用反转录聚合酶链反应（RT-PCR）、酶联免疫吸附试验（ELISA）和免疫荧光法研究了它们对HBV表达的抑制作用。体外诱导了 miMSC-shRNA 的肝脏分化，并通过形态学、反转录半定量和定量 PCR、尿素生成和周期性酸-希夫染色分析进行了确认。前者成功抑制了血清和肝组织中的 HBV 表达，而后者仅抑制了肝组织中的 HBV 表达。对血清丙氨酸氨基转移酶水平、天门冬氨酸氨基转移酶水平、肝脏重量/体重比率百分比和西里斯红染色的分析表明，两种治疗方案都能明显改善小鼠的肝损伤。本研究结果表明，miMSCs 结合 shRNA 治疗可减轻肝损伤并抑制 HBV 表达，从而为治疗 HBV 感染引起的肝损伤提供了一种新的潜在治疗策略。
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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影响因子：
6
作者：
Oh IS;Park SH
通讯作者：
Park SH
影响因子：
3.6
作者：
Liu J;Pan G;Liang T;Huang P
通讯作者：
Huang P
影响因子：
13.5
作者：
Higashiyama, Reiichi;Inagaki, Yutaka;Okazaki, Isao
通讯作者：
Okazaki, Isao
影响因子：
12.4
作者：
Chen, Chun-Chi;Sun, Cheng-Pu;Tao, Mi-Hua
通讯作者：
Tao, Mi-Hua
影响因子：
3.9
作者：
Rabani, Vahideh;Shahsavani, Mansoureh;Baharvand, Hossein
通讯作者：
Baharvand, Hossein