Therapeutic effects of hepatocyte growth factor-overexpressing dental pulp stem cells on liver cirrhosis in a rat model.
Therapeutic effects of hepatocyte growth factor-overexpressing dental pulp stem cells on liver cirrhosis in a rat model.
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过表达肝细胞生长因子的牙髓干细胞对肝硬化大鼠模型的治疗作用
DOI：
10.1038/s41598-017-14995-5
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发表时间：
2017-11-17
影响因子：
4.6
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Cao XF;Jin SZ;Sun L;Zhan YB;Lin F;Li Y;Zhou YL;Wang XM;Gao L;Zhang B
肝硬化是肝脏疾病的终末期，容易发展为肝细胞癌。越来越多的证据表明，牙髓干细胞（DPSC）的移植可能会促进肝硬化的恢复，但涉及的关键调控机制仍有待确定。在本研究中，我们在原代大鼠DPSCs中过表达人肝细胞生长因子（hHGF），并评估HGF过表达对肝硬化DPSCs移植的生物学行为和治疗效果的影响。通过每周两次腹腔注射CCl 4诱导肝硬化，共12周，并通过组织病理学和血清学检测进行验证。通过用hHGF-慢病毒载体转导，HGF在DPSC中过表达，并基于HGF的表达和分泌升高来证实。将过表达HGF的DPSCs经静脉移植到大鼠体内。在移植后6周，HGF过表达的DPSCs在宿主肝组织中的存活率和肝细胞分化增加。与在生理水平表达HGF的DPSC相比，它们还表现出与肝硬化病理和肝功能受损相关的显著更大的修复潜力。本研究为临床开发肝硬化治疗新方法提供了实验依据。
Cirrhosis is the terminal stage of hepatic diseases and is prone to develop into hepatocyte carcinoma. Increasing evidence suggests that the transplantation of dental pulp stem cells (DPSCs) may promote recovery from cirrhosis, but the key regulatory mechanisms involved remain to be determined. In this study, we overexpressed human hepatocyte growth factor (hHGF) in primary rat DPSCs and evaluated the effects of HGF overexpression on the biological behaviors and therapeutic efficacy of grafted DPSCs in cirrhosis. Liver cirrhosis was induced via the intraperitoneal injection of CCl4twice weekly for 12 weeks and was verified through histopathological and serological assays. HGF was overexpressed in DPSCs via transduction with a hHGF-lentiviral vector and confirmed based on the elevated expression and secretion of HGF. The HGF-overexpressing DPSCs were transplanted into rats intravenously. The HGF-overexpressing DPSCs showed increased survival and hepatogenic differentiation in host liver tissue at 6 weeks after grafting. They also exhibited a significantly greater repair potential in relation to cirrhosis pathology and impaired liver function than did DPSCs expressing HGF at physiological levels. Our study may provide an experimental basis for the development of novel methods for the treatment of liver cirrhosis in clinical practice.
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影响因子：
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通讯作者：
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