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, People's Republic of China.
J Mol Med (Berl). 2019 Aug;97(8):1065-1084. doi: 10.1007/s00109-019-01804-x. Epub 2019 Jun 13.
After the death of large numbers of cells in liver tissue is triggered by various hepatotoxic factors, intimidating and life-threatening acute liver failure (ALF) can develop with high mortality and expensive costs. Although liver transplantation and hepatocyte transplantation have become substitutes for improving liver regeneration, their applications are inhibited by scarce tissue and cell resources. Therefore, the transplantation of mesenchymal stromal cells (MSCs) and their derivatives including hepatocyte-like cells (HLCs), conditioned medium (CM), and exosomes (Ex) can help alleviate liver injury in ALF individuals or animal models via engraftment into liver tissue, hepatogenic differentiation, the promotion of host hepatocyte proliferation, the secretion of anti-inflammatory factors and antioxidants, and the enhancement of liver regeneration in vivo. In addition, biomaterial scaffolds protect MSCs against a harsh microenvironment in vitro and in vivo, in addition to providing physical and directional support for liver regeneration. In this review, we aimed to discuss the underlying mechanisms and therapeutic effects of MSCs and their derivatives on rescuing ALF animal models according to current studies. Further breakthroughs are required to establish safer, more stable, and more effective stem cell-based therapy in regenerative medicine for repairing liver injury, thus reducing the morbidity and mortality of ALF in the near future.
在大量细胞因各种肝毒性因素而死亡后,可能会引发危及生命的急性肝衰竭(ALF),其死亡率高且治疗费用昂贵。虽然肝移植和肝细胞移植已成为改善肝脏再生的替代方法,但由于组织和细胞资源稀缺,其应用受到限制。因此,间充质基质细胞(MSCs)及其衍生物(包括肝样细胞(HLCs)、条件培养基(CM)和外泌体(Ex))的移植可通过植入肝组织、肝向分化、促进宿主肝细胞增殖、分泌抗炎和抗氧化因子以及增强体内肝脏再生,有助于缓解 ALF 个体或动物模型的肝损伤。此外,生物材料支架可保护 MSCs 免受体外和体内恶劣的微环境影响,同时为肝脏再生提供物理和定向支持。在这篇综述中,我们旨在根据现有研究讨论 MSCs 及其衍生物在拯救 ALF 动物模型方面的潜在机制和治疗效果。需要进一步的突破来建立更安全、更稳定和更有效的基于干细胞的再生医学疗法,以在不久的将来降低 ALF 的发病率和死亡率。