Development and Validation of a Scaffold-Free Human Multilineage Spheroid Model for Early Stage Cholangiopathies Driven by Cholangiocyte Senescence.

ABSTRACT:

Background and aims

Cholangiopathies, including primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), and post-COVID-19 cholangiopathy (PCC), involve chronic cholangiocyte injury, senescence, epithelial-stromal crosstalk, and progressive fibrosis. However, effective in vitro models to capture these interactions are limited. Here, we present a scaffold-free 3D multilineage spheroid model, composed of hepatocyte-like cells (HepG2), cholangiocytes (H69), and hepatic stellate cells (LX-2), designed to recapitulate early fibrogenic responses driven by senescent cholangiocytes.

Methods

Cholangiocyte senescence was induced via ionising radiation prior to spheroid assembly. Fibrosis progression was assessed by mRNA expression of hepatic stellate cell (HSC) activat

SUBMITTER: Wu CT 

PROVIDER: S-EPMC12423616 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature