Department of Dentistry, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China.
Department of Gastrointestinal and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China.
Sci Rep. 2017 Nov 17;7(1):15812. doi: 10.1038/s41598-017-14995-5.
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 CCl twice 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.
肝硬化是肝脏疾病的终末期阶段，容易发展为肝细胞癌。越来越多的证据表明，牙髓干细胞（DPSCs）的移植可能促进肝硬化的恢复，但涉及的关键调节机制仍有待确定。在这项研究中，我们在原代大鼠 DPSCs 中转染人肝细胞生长因子（hHGF），并评估 HGF 过表达对移植 DPSCs 在肝硬化中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 诱导肝硬化 12 周，并通过组织病理学和血清学检测进行验证。通过 hHGF 慢病毒载体转导在 DPSCs 中过表达 HGF，并基于 HGF 的高表达和分泌进行确认。将 HGF 过表达的 DPSCs 静脉移植到大鼠体内。移植后 6 周，HGF 过表达的 DPSCs 在宿主肝组织中表现出更高的存活率和肝向分化。与表达生理水平 HGF 的 DPSCs 相比，它们在肝硬化病理和肝功能受损方面表现出更大的修复潜力。我们的研究可能为临床实践中治疗肝硬化的新方法的发展提供实验基础。
