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Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

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Hepatocellular carcinoma (HCC) is a very common form ofcancer worldwide and is often fatal. Although the histopathologyof HCC is characterized by metabolic pathophysiology,fibrosis, and cirrhosis, the focus of treatment has been on eliminatingHCC. Recently, three-dimensional (3D) multicellularhepatic spheroid (MCHS) models have provided a) new therapeuticstrategies for progressive fibrotic liver diseases, such asantifibrotic and anti-inflammatory drugs, b) molecular targets,and c) treatments for metabolic dysregulation. MCHS modelsprovide a potent anti-cancer tool because they can mimic a)tumor complexity and heterogeneity, b) the 3D context of tumorcells, and c) the gradients of physiological parameters that arecharacteristic of tumors in vivo. However, the information providedby an multicelluar tumor spheroid (MCTS) model mustalways be considered in the context of tumors in vivo. Thismini-review summarizes what is known about tumor HCCheterogeneity and complexity and the advances provided byMCHS models for innovations in drug development to combatliver diseases.

Abstract

Hepatocellular carcinoma (HCC) is a very common form ofcancer worldwide and is often fatal. Although the histopathologyof HCC is characterized by metabolic pathophysiology,fibrosis, and cirrhosis, the focus of treatment has been on eliminatingHCC. Recently, three-dimensional (3D) multicellularhepatic spheroid (MCHS) models have provided a) new therapeuticstrategies for progressive fibrotic liver diseases, such asantifibrotic and anti-inflammatory drugs, b) molecular targets,and c) treatments for metabolic dysregulation. MCHS modelsprovide a potent anti-cancer tool because they can mimic a)tumor complexity and heterogeneity, b) the 3D context of tumorcells, and c) the gradients of physiological parameters that arecharacteristic of tumors in vivo. However, the information providedby an multicelluar tumor spheroid (MCTS) model mustalways be considered in the context of tumors in vivo. Thismini-review summarizes what is known about tumor HCCheterogeneity and complexity and the advances provided byMCHS models for innovations in drug development to combatliver diseases.

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