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.

A Human Liver‐on‐a‐Chip Platform for Modeling Nonalcoholic Fatty Liver Disease

“…Analysis of albumin secretion for HepG2 cultured for 8 days in spheroids displayed a continuous increase in secretion, independently of the presence of both HUVECs and FFAs, indicating that our chip system provides an ideal microenvironment for the spheroids (Figure J; Figure S7, Supporting Information). Furthermore, the multicellular spheroids showed higher levels of albumin secretion over 8 days compared to those without HUVECs (≈2‐fold and ≈1.6‐fold for without and with FFAs), which is in accordance with previous reports exhibiting coculturing HUVECs with hepatocytes induced increased levels of albumin secretion . We also observed a notable difference of secretion in spheroids only composed of HepG2 under fat conditions (≈1.25‐fold higher than those without FFAs) as shown in a previous study, whereas albumin expression was not different when HUVECs interacted with HepG2 in spheroids.…”

“…Coculturing hepatocytes with NPCs could add a level of complexity resulting in a better mimicking of the in vivo hepatic lobule. Indeed, inclusion of NPCs in hepatic culture systems has been shown to enhance hepatocyte biosynthetic functions and metabolic response to drug treatment . For instance, sinusoidal endothelial cells—important for vascularization—improved functionality of hepatocytes such as cytochrome P450 (CYP450) activity and albumin secretion, providing optimal trophic support for the hepatocytes .…”

“…Indeed, inclusion of NPCs in hepatic culture systems has been shown to enhance hepatocyte biosynthetic functions and metabolic response to drug treatment . For instance, sinusoidal endothelial cells—important for vascularization—improved functionality of hepatocytes such as cytochrome P450 (CYP450) activity and albumin secretion, providing optimal trophic support for the hepatocytes . Another study by Ehrlich et al developed a sensor‐integrated liver on chip array using human liver organoids composed of albumin‐positive E6/E7LOW hepatocytes and endothelial cells, monitoring oxygen while glucose, lactate, and temperature were measured in real time using microfluidic electrochemical sensors.…”

Is It Time to Start Transitioning From 2D to 3D Cell Culture?

“…Not only do organ chip models allow for better organ models, but they also permit high-resolution and real-time imaging making it easier to analyze in vitro biochemical, genetic, and metabolic activities present in human tissue (Sontheimer-Phelps et al, 2019). Some human organs that have been successfully modeled on organ chip devices include: kidney tubules (Maschmeyer et al, 2015), small intestine (Kasendra et al, 2018), bronchioles (Benam et al, 2016), liver (Beckwitt et al, 2018), BBB (Adriani et al, 2017), lung alveoli (Stucki et al, 2015), and bone marrow (Sieber et al, 2018). Not only can these organs be modeled, but more importantly they can give accurate organ-level responses to many stimuli including drugs (Hassell et al, 2017), toxins (66), radiation , cigarette smoke (Benam et al, 2016), and pathogens (Kim et al, 2016).…”

In Vitro Human Liver Model of Nonalcoholic Steatohepatitis by Coculturing Hepatocytes, Endothelial Cells, and Kupffer Cells

“…In addition, an in vitro human model of NAFLD was proposed by Kostrzewski et al in which a 3D perfused culture system employed primary hepatocytes that were supplied with either lean or fat culture media . However, modeling the continuous NAFLD pathogenesis, especially NASH, has been much more challenging because of the complexity of the liver microenvironment that involve numerous cellular communications between parenchymal (hepatocytes) and nonparenchymal cells (endothelial, KCs, and stellate) …”