Journal of Clinical Hepatology
This article discusses the therapeutic effects and mechanisms of human umbilical cord mesenchymal stem cells (hUC-MSC) with overexpression of Numb gene on bile duct obstruction liver fibrosis (CLF). The study used bile duct ligation (BDL) to construct a rat CLF model and compared the efficacy of unloaded control (hUC-MSC) and Numb overexpression groups. The results show that hUC-MSC is significantly superior to ordinary hUC-MSC, which can more effectively reduce serum liver enzymes, bile acids, fibrosis indicators (Hyp, α-SMA), inflammatory factors (TNF-α, TGF-β1), and bile duct reaction markers (CK7/CK19), while improving liver regeneration indicators (Alb, HNF4α) and activating the Numb-p53-HNF4α signaling axis. Mechanically, Numb promotes the differentiation of hUC-MSC into liver-like cells by regulating the stability of p53-Mdm2, enhancing liver regeneration capacity.
This study provides a new intervention paradigm based on "gene-enhanced stem cells" for the treatment of CLF, a refractory liver disease, and breaks through the bottleneck of limited efficacy of traditional stem cell therapy. For the first time, it reveals the key role of the Numb-PTBL-p53-HNF4α axis in stem cell liver differentiation and liver regeneration, not only deepening the understanding of the function of Numb in liver homeostasis (supplementing the p53-dependent pathway outside of Notch regulation) but also providing clear molecular targets and experimental evidence for optimizing stem cell treatment strategies and promoting clinical transformation.
Objective: To investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell (hUC-MSC) with over…
