Liver organ-on-chip models for toxicity studies and risk assessment
Résumé
The liver is a key organ that plays a pivotal role in metabolism and ensures a variety of functions in the
body, including homeostasis, synthesis of essential components, nutrient storage, and detoxification. As the
centre of metabolism for exogenous molecules, the liver is continuously exposed to a wide range of
compounds, such as drugs, pesticides, and environmental pollutants. Most of these compounds can cause
hepatotoxicity and lead to severe and irreversible liver damage. To study the effects of chemicals and drugs
on the liver, most commonly, animal models or in vitro 2D cell cultures are used. However, data obtained
from animal models lose their relevance when extrapolated to the human metabolic situation and pose
ethical concerns, while 2D static cultures are poorly predictive of human in vivo metabolism and toxicity.
As a result, there is a widespread need to develop relevant in vitro liver models for toxicology studies. In
recent years, progress in tissue engineering, biomaterials, microfabrication, and cell biology has created
opportunities for more relevant in vitro models for toxicology studies. Of these models, the liver organ-onchip
(OoC) has shown promising results by reproducing the in vivo behaviour of the cell/organ or a group
of organs, the controlled physiological micro-environment, and in vivo cellular metabolic responses. In this
review, we discuss the development of liver organ-on-chip technology and its use in toxicity studies. First,
we introduce the physiology of the liver and summarize the traditional experimental models for toxicity
studies. We then present liver OoC technology, including the general concept, materials used, cell sources,
and different approaches. We review the prominent liver OoC and multi-OoC integrating the liver for drug
and chemical toxicity studies. Finally, we conclude with the future challenges and directions for developing
or improving liver OoC models.
Origine | Fichiers produits par l'(les) auteur(s) |
---|