Immortalized Human Hepatic Stellate Cells-SV40T

Immortalized Human Hepatic Stellate Cells (HSCs) engineered via stable expression of the SV40 Large T antigen (SV40T) represent a robust, genetically defined experimental platform that overcomes the finite lifespan, inter-donor variability, and ethical constraints inherent to primary human HSC cultures. By overriding cell-cycle arrest through SV40T-mediated inactivation of p53 and pRB pathways, these cells achieve unlimited proliferative capacity while retaining the activated myofibroblastic phenotype characteristic of pathological HSC transdifferentiation.

A principal advantage of SV40T-immortalized human HSCs is their faithful preservation of key functional and molecular hallmarks. These cells consistently express canonical activation markers including α-smooth muscle actin (α-SMA), vimentin, glial fibrillary acidic protein (GFAP), platelet-derived growth factor receptor-β (PDGFRβ), discoidin domain receptor 2 (DDR2), and the leptin receptor (Ob-R). Functionally, they secrete type I procollagen, pro-MMP-2, MT1-MMP, TIMP-1, and TIMP-2, and retain the capacity to absorb, accumulate, and esterify retinol—mimicking critical aspects of native HSC biology in hepatic fibrogenesis and retinoid metabolism.

These cells exhibit robust responsiveness to canonical fibrogenic stimuli: TGF-β1 potently upregulates collagen expression, while PDGF-B drives proliferation. Their high transfection efficiency further enables mechanistic studies involving gene overexpression, knockdown, and CRISPR/Cas9-mediated genome editing. Authenticated by STR profiling and extensively characterized in peer-reviewed literature, SV40T-immortalized human HSCs provide a standardized, reproducible, and scalable resource for investigating liver fibrosis pathogenesis, anti-fibrotic drug screening, extracellular matrix dynamics, and cytokine signaling pathways.