Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells

Cell therapy shows great promise as an alternative therapy for the cirrhotic liver. We have previously developed an approach for efficient expansion of both murine and human hepatocyte-derived liver progenitor-like cells (HepLPCs) in vitro without genetic modification. The current study aimed to apply HepLPCs to treatment of liver cirrhosis. The effects of allogeneic HepLPCs transplantation were studied in rat models of liver cirrhosis induced by carbon tetrachloride (CCl4) . Liver tissues were collected and analyzed by RNA sequencing array to analyze changes in histology or gene expression patterns. Transplantation of HepLPCs reduced active fibrogenesis and net fibrosis in model of liver cirrhosis. Apoptosis of hepatic stellate cells (HSCs) was observed in vivo after HepLPCs treatment. Overall design: Comparative gene expression profiling analysis of RNA-seq data for whole liver samples of control rats (normal) or rats injected with PBS or rat HepLPCs, n=3. Control livers were obtained from animals that received neither CCl4 nor cell transplants.

细胞疗法为肝硬化的治疗提供了极具潜力的替代方案。本课题组此前已建立一种无需基因修饰，即可在体外高效扩增小鼠及人肝细胞来源的肝祖细胞样细胞（HepLPCs）的方法。本研究旨在将HepLPCs应用于肝硬化的治疗研究。
本研究采用四氯化碳（CCl4）诱导的肝硬化大鼠模型，探究同种异体HepLPCs移植的治疗效果。研究人员收集各组大鼠的肝脏组织，通过RNA测序阵列分析组织学特征与基因表达模式的变化。结果显示，HepLPCs移植可减轻肝硬化模型中的活动性纤维生成与净纤维化程度；经HepLPCs治疗后，体内可观察到肝星状细胞（HSCs）的凋亡现象。
实验设计概述：对三组大鼠的全肝样本开展RNA测序（RNA-seq）数据的比较基因表达谱分析，三组分别为正常对照组大鼠、经磷酸盐缓冲液（PBS）注射的肝硬化模型大鼠，以及经大鼠HepLPCs移植的肝硬化模型大鼠，每组n=3。正常对照组的肝脏组织取自未接受CCl4处理与细胞移植的大鼠。