Deng Liping, Wu Bingjie, Liang Kaini, Liao Hongen, Du Yanan
Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 10084, China.
ILIVER. 2022 Nov 19;1(4):265-274. doi: 10.1016/j.iliver.2022.11.002. eCollection 2022 Dec.
Liver fibrosis is typically caused by chronic viral hepatitis and, more recently, fatty liver disease associated with obesity. There are currently no approved drugs for liver cirrhosis, and liver transplantation is limited by donor scarcity, thus driving the investigation of novel therapeutic strategies. The development of liver fibrosis presents with stage- and zone-dependent characteristics that manifest as distinct dynamic changes during vascularization and extracellular matrix (ECM) deposition. However, current cellular therapies do not consider the spatiotemporal variations of liver fibrosis without identifying the precise location and stage to administer the intervention to achieve optimal therapeutic effects. Herein, we focus on endothelial cell (EC) and macrophage therapy for liver fibrosis because of their important roles in regulating the spatiotemporal changes of vascularization and ECM deposition during liver fibrosis progression. Overall, this review summarizes the stage-dependent EC and macrophage therapy for liver fibrosis, elucidates their respective mechanisms, and exemplifies potential strategies to realize precise cell therapy by targeting specific liver zones.
肝纤维化通常由慢性病毒性肝炎引起，近来也与肥胖相关的脂肪性肝病有关。目前尚无获批用于肝硬化的药物，肝移植又受供体稀缺的限制，因此推动了新型治疗策略的研究。肝纤维化的发展具有阶段和区域依赖性特征，在血管生成和细胞外基质（ECM）沉积过程中表现为明显的动态变化。然而，目前的细胞疗法并未考虑肝纤维化的时空变化，未确定进行干预以实现最佳治疗效果的精确位置和阶段。在此，我们聚焦于内皮细胞（EC）和巨噬细胞治疗肝纤维化，因为它们在肝纤维化进展过程中调节血管生成和ECM沉积的时空变化方面发挥着重要作用。总体而言，本综述总结了针对肝纤维化的阶段依赖性EC和巨噬细胞治疗，阐明了它们各自的机制，并举例说明了通过靶向特定肝区实现精确细胞治疗的潜在策略。
