Possibility of the Enhanced Progression of Fetal Liver Stem/Progenitor Cells Therapy for Treating End-stage Liver Diseases by Regulating the Notch Signaling Pathway

Abstract

Cell therapy is the most promising therapy for end-stage liver diseases (ESLDs). Fetal liver stem/progenitor cells (FLSPCs) have the advantages of a high survival rate, high proliferation, small volume, and high safety, which make them one of the ideal cells for stem cell therapy for liver diseases. During the early phase of our study, we applied a three-step separation method to enrich FLSPCs and obtained a separation efficiency that was similar to the flow cell-sorting method. Additionally, using a fulminant hepatic failure rat model, we demonstrated that FLSPCs can contribute to the recovery of hepatic morphogenesis and function. However, two problems remain to be resolved to explore the therapeutic potential of FLSPCs. First, how can FLSPCs be induced to accurately differentiate into hepatocytes and cholangiocytes? Second, how do FLSPCs maintain self-renewal? The Notch signaling plays a critical role in regulating the differentiation and self-renewal of many types of stem cells. Additionally, our previous findings have shown that the Notch signaling plays an important role in FLSPC differentiation into hepatocytes. Therefore, we hypothesized that the Notch signaling may be involved in the differentiation and self-renewal of FLSPCs. We began a study on the regulatory effects and relative molecular mechanisms of the Notch signaling on FLSPCs and found the corresponding interfering target, which may become an index for the clinical application of FLSPCs.