The development of new therapies for hepatitis B is dependent on scalable, durable models that accurately recapitulate human physiology and HBV infection. In a new study, Ortega-Prieto et al. designed a 3D microfluidic system to culture primary human hepatocytes (PHHs). The system, consisting of a perfused bioreactor and collagen-coated polystyrene scaffolds seeded with PHHs, was able to maintain PHH morphology, viability and synthesis of hepatocyte-specific markers for at least 40 days. Importantly, PHHs cultured in this fashion were readily infected by patient-derived HBV; compared with existing models such as hepatic spheroids, 10,000-fold lower levels of HBV were required to infect PHHs cultured in the new system. PHH responses to HBV infection were also found to reflect host responses in patient or chimpanzee tissue samples.
Ortega-Prieto, A. M. et al. 3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection. Nat. Commun. 9, 682 (2018)
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Thomas, H. A new model for HBV infection of primary human hepatocytes. Nat Rev Gastroenterol Hepatol 15, 190 (2018). https://doi.org/10.1038/nrgastro.2018.21