No abstract

The liver is the most important metabolic organ in the body. Model systems that recapitulate the complex organ structure and cell composition of the human liver are insufficient to study liver biology and to test toxicity and efficacy during new drug development. Recently established 3-dimensional liver models, including spheroids and organoids, organs-on-a-chip, bioprinting, and the decellularization/recellularization technique, have provided platforms that emulate the structural and functional characteristics of the human liver better than conventional 2-dimensional cell culture models and animal models. This review summarizes the architecture and cell compositions of human liver tissue, focusing on recent studies of multicellular human liver models that recapitulate in vivo-like physiologies with morphological and functional advances by the cellular communication of parenchymal and non-parenchymal cells. We discuss the applications, limitations, and future perspectives of advanced multicellular human liver models.

Drug safety issues continue to occur even with drugs that are approved after the completion of clinical studies. Drug-induced liver injury (DILI) is a major obstacle to drug development, because the liver is the primary site of drug metabolism, and injuries caused during this process are severe. Conventional in vitro human liver models, such as 2-dimensional hepatic cell lines, lack in vivo physiological relevance, and animal studies have limitations in the form of species differences and regulatory restrictions. To resolve this issue, an increasing number of 3-dimensional human liver systems, including organoids, are being developed. In this review, we provide an overview of recent assessments of DILI prediction, approaches for in vitro hepatotoxicity evaluation, and a variety of advanced human liver models. We discuss the advantages, limitations, and future perspectives of current human liver models for accurate drug safety evaluations.