Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Cell Death Dis. 2021 Jan 21;12(1):111. doi: 10.1038/s41419-020-03374-0.
Hepatectomy is an effective therapeutic strategy for many benign and malignant liver diseases, while the complexity of liver anatomy and the difficulty of operation lead to complications after hepatectomy. Among them, post-hepatectomy liver failure (PHLF) is the main factor threatening the life of patients. At present, liver transplantation is an effective approach for PHLF. However, the application of liver transplantation has been largely limited due to the shortage of donors and the high cost of such operation. Therefore, it is urgently necessary to develop a new treatment for PHLF. Mesenchymal stem cells (MSCs) have become a new treatment regimen for liver diseases because of their easy access and low immunogenicity. Our study found that there were some subtle connections between MSCs and liver lipid metabolism in the PHLF model. We used MSC transplantation to treat PHLF induced by 90% hepatectomy. MSC transplantation could restore the mitochondrial function, promote the β-oxidation of fatty acid (FA), and reduce the lipid accumulation of hepatocytes. In addition, interleukin 10 (IL-10), a cytokine with immunoregulatory function, had an important role in lipid metabolism. We also found that MSCs transplantation activated the mammalian target of rapamycin (mTOR) pathway. Therefore, we explored the relationship between mitochondrial damage and lipid metabolism abnormality or PHLF. MSCs improved mitochondrial function and corrected abnormal lipid metabolism by affecting the mTOR pathway in the treatment of PHLF. Collectively, MSC transplantation could be used as a potential treatment for PHLF.
肝切除术是治疗许多良性和恶性肝脏疾病的有效治疗策略,然而肝脏解剖结构的复杂性和手术难度导致肝切除术后出现并发症。其中,肝切除术后肝功能衰竭(PHLF)是威胁患者生命的主要因素。目前,肝移植是治疗 PHLF 的有效方法。然而,由于供体短缺和手术费用高昂,肝移植的应用受到了很大限制。因此,迫切需要开发新的 PHLF 治疗方法。间充质干细胞(MSCs)因其易于获取和低免疫原性而成为治疗肝脏疾病的新方案。我们的研究发现,在 PHLF 模型中,MSCs 与肝脏脂质代谢之间存在一些微妙的联系。我们使用 MSC 移植治疗 90%肝切除诱导的 PHLF。MSC 移植可以恢复线粒体功能,促进脂肪酸(FA)的β氧化,减少肝细胞的脂质积累。此外,具有免疫调节功能的细胞因子白细胞介素 10(IL-10)在脂质代谢中起着重要作用。我们还发现 MSC 移植激活了哺乳动物雷帕霉素靶蛋白(mTOR)通路。因此,我们探讨了线粒体损伤与脂质代谢异常或 PHLF 之间的关系。MSCs 通过影响 mTOR 通路改善线粒体功能并纠正异常脂质代谢,从而在治疗 PHLF 中发挥作用。综上所述,MSC 移植可作为 PHLF 的一种潜在治疗方法。