• BMB Reports
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• v.56 no.4
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• pp.225-233
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• 2023

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.137-144
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• 1994

Spherical multicellular aggregates of adult rat hepatocytes (spheroid) which have tissue like structure, were formed and immobilized in the pores of polyurethane foam (PUF) which was used as a culture substratum. These hepatocyte/spheroids, about 100 $\mu\textrm{m}$ in diameter, have maintained higher differentiated functions than those of hepatocyte/monolayer for about 3 weeks in serum-free medium. Then, we designed a prototype module of an artificial liver support system using a PUF/spheroid packed-bed, in which hepatocyte/spheroids were immobilized at high density. The urea synthesis activity of the artificial liver was maintained at least 10 days in 100% rat blood plasma. We start examining the performance of hybrid artificial liver in an ex vivo extracorporeal experiment with an acute hepatic failure rat.