Directing Cholangiocyte Morphogenesis in Natural Biomaterial Scaffolds.
Quinton SmithJennifer BaysLinqing LiHaniyah ShareefChristopher S ChenSangeeta N BhatiaPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2021)
Patients with Alagille syndrome carry monogenic mutations in the Notch signaling pathway and face complications such as jaundice and cholestasis. Given the presence of intrahepatic ductopenia in these patients, Notch2 receptor signaling is implicated in driving normal biliary development and downstream branching morphogenesis. As a result, in vitro model systems of liver epithelium are needed to further mechanistic insight of biliary tissue assembly. Here, primary human intrahepatic cholangiocytes as a candidate population for such a platform are systematically evaluated, and conditions that direct their branching morphogenesis are described. It is found that extracellular matrix presentation, coupled with mitogen stimulation, promotes biliary branching in a Notch-dependent manner. These results demonstrate the utility of using 3D scaffolds for mechanistic investigation of cholangiocyte branching and provide a gateway to integrate biliary architecture in additional in vitro models of liver tissue.
Keyphrases
- extracellular matrix
- end stage renal disease
- signaling pathway
- cell proliferation
- tissue engineering
- ejection fraction
- endothelial cells
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- prognostic factors
- epithelial mesenchymal transition
- risk factors
- pi k akt
- high throughput
- nuclear factor
- toll like receptor
- single cell
- induced apoptosis