Liver 'organ on a chip'

Abstract

The liver plays critical roles in both homeostasis and pathology. It is the major site of drug metabolism in the body and, as such, a common target for drug-induced toxicity and is susceptible to a wide range of diseases. In contrast to other solid organs, the liver possesses the unique ability to regenerate. The physiological importance and plasticity of this organ make it a crucial system of study to better understand human physiology, disease, and response to exogenous compounds. These aspects have impelled many to develop liver tissue systems for study in isolation outside the body. Herein, we discuss these biologically engineered organoids and microphysiological systems. These aspects have impelled many to develop liver tissue systems for study in isolation outside the body. Herein, we discuss these biologically engineered organoids and microphysiological systems.

Keywords: 3D culture systems; Microphysiologic systems; Organoids.

Figure 1

(A) The architecture of the hepatic sinusoid. Blood enters the portal triad region of the liver through a hepatic arteriole and portal venule and traverses the hepatic sinusoid to the central vein, whereby it is drained into the larger hepatic central veins. The sinusoidal endothelial cells mediate blood flow and are fenestrated to allow rapid diffusion of nutrients, signaling factors, and drug compounds. The hepatocytes compose the parenchyma of the liver and sit deep to the endothelium. The hepatic stellate cells reside in the Space of Disse, a zone between the endothelium and hepatocytes. Finally, the Kupffer cells line the inside of the sinusoid and mediate antigen sensing and intercellular communication. (B) A schematic of the three dimensional liver tissues as presented within the LiverChip, that are subject to fluid flow in micro-scale pores of a scaffold, which facilitates shear stresses and establishment of a physiological oxygen gradient.