Dear Colleagues,

Traditional hepatotoxicity testing has relied heavily on in vivo experimentations which are expensive and restrictive with regard to very important ethical implications. In addition, these studies often yield data that are not relevant to human exposures or biological responses due to intra-species variations, necessitating the requirement for further testing or candidate (drug) abandonment in late development stages. There is increasing global pressure from society (e.g., pressure for a ban on animal testing), regulatory agencies and the scientific community to develop physiologically relevant in vitro alternatives for testing that can be utilized for mechanistic dose response hazard identification.

One of the conventional challenges with in vitro hepatic cell culture is the fact that human primary hepatocytes have a relatively short half-life in 2D culture systems and often lose their liver-specific functions over time. In recent years, considerable improvements in the in vitro long-term maintenance of liver function has been made possible principally due the development of improved cell culture techniques, principally via the utilization of 3D culture models. These systems provide a microenvironment in which cell–cell and cell–matrix contact mimic the physiological liver architecture. Although hepatocytes have been the primary research focus for toxic responses in the liver, it is becoming increasingly clear that non-parenchymal cells (NPCs) are essential in the liver in both homeostasis and disease and that they play a critical role in the in vivo response to xenobiotic insult. NPCs are also fundamental in mitigating hepatic injury inflicted by xenobiotics by triggering repair processes up to complete liver regeneration after major trauma or surgical resections. This also holds true for the progression of fatty liver disease. Liver injury repair response and tissue re-modeling might compromise the ability of hepatocytes to adequately respond to prolonged metabolic or xenobiotic stress.

In this Special Issue, we invite original research and reviews focusing on physiological and pathophysiological hepatic in vitro systems designed for next-generation drug, chemical and (nano)particulate toxicological assessment.

Dr. Ali Kermanizadeh
Dr. Wolfgang Moritz
Guest Editors

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• liver
• advanced physiological and pathophysiological hepatic in vitro systems
• non-parenchymal cells
• toxicology
• hepatotoxicity
• drugs
• chemicals
• particulates