Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, PR China.
Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.
J Cell Mol Med. 2019 Mar;23(3):1657-1670. doi: 10.1111/jcmm.14115. Epub 2019 Jan 11.
End-stage liver fibrosis frequently progresses to portal vein thrombosis, formation of oesophageal varices, hepatic encephalopathy, ascites, hepatocellular carcinoma and liver failure. Mesenchymal stem cells (MSCs), when transplanted in vivo, migrate into fibrogenic livers and then differentiate into hepatocyte-like cells or fuse with hepatocytes to protect liver function. Moreover, they can produce various growth factors and cytokines with anti-inflammatory effects to reverse the fibrotic state of the liver. In addition, only a small number of MSCs migrate to the injured tissue after cell transplantation; consequently, multiple studies have investigated effective strategies to improve the survival rate and activity of MSCs for the treatment of liver fibrosis. In this review, we intend to arrange and analyse the current evidence related to MSC transplantation in liver fibrosis, to summarize the detailed mechanisms of MSC transplantation for the reversal of liver fibrosis and to discuss new strategies for this treatment. Finally, and most importantly, we will identify the current problems with MSC-based therapies to repair liver fibrosis that must be addressed in order to develop safer and more effective routes for MSC transplantation. In this way, it will soon be possible to significantly improve the therapeutic effects of MSC transplantation for liver regeneration, as well as enhance the quality of life and prolong the survival time of patients with liver fibrosis.
终末期肝纤维化常进展为门静脉血栓形成、食管静脉曲张、肝性脑病、腹水、肝细胞癌和肝功能衰竭。间充质干细胞(MSCs)在体内移植后,迁移到纤维性肝脏,然后分化为肝细胞样细胞或与肝细胞融合以保护肝功能。此外,它们可以产生具有抗炎作用的各种生长因子和细胞因子,以逆转肝脏的纤维化状态。此外,细胞移植后只有少数 MSCs 迁移到受损组织;因此,多项研究已经探讨了提高 MSCs 存活率和活性以治疗肝纤维化的有效策略。在这篇综述中,我们旨在整理和分析与 MSCs 移植治疗肝纤维化相关的现有证据,总结 MSCs 移植逆转肝纤维化的详细机制,并讨论这种治疗的新策略。最后,也是最重要的,我们将确定基于 MSC 的疗法治疗肝纤维化所必须解决的当前问题,以开发更安全、更有效的 MSC 移植途径。这样,就有可能显著提高 MSCs 移植治疗肝再生的治疗效果,提高肝纤维化患者的生活质量和延长生存时间。