The potential of organoids in toxicologic pathology: role of toxicologic pathologists in <i>in vitro</i> chemical hepatotoxicity assessment

Abstract

The development of in vitro toxicity assessment methods using cultured cells has gained popularity for promoting animal welfare in animal experiments. Herein, we briefly discuss the current status of hepatoxicity assessment using human- and rat-derived hepatocytes; we focus on the liver organoid method, which has been extensively studied in recent years, and discuss how toxicologic pathologists can use their knowledge and experience to contribute to the development of in vitro chemical hepatotoxicity assessment methods for drugs, pesticides, and chemicals. We also propose how toxicological pathologists should assess toxicity regarding the putative distribution of undifferentiated and differentiated cells in the organoid when liver organoids are observed in hematoxylin and eosin–stained specimens. This was done while considering the usefulness and limitations of in vitro studies for toxicologic pathology assessment.

Establishment of an experimental model of canine apocrine gland anal sac adenocarcinoma organoid culture using a three-dimensional culture method

“…Tumor organoids excel in reproducing the histopathological, genetic, and phenotypic characteristics of patient-derived tumor tissues [20,21], and this technology has been used in human pancreatic, prostate, ovarian, bladder, liver, breast, lung, esophageal, stomach, colon, endometrial, kidney, and brain tumors. Organoid biobanks have also been constructed [22][23][24][25][26][27][28][29][30][31]. Organoids have also been used to study cancer in companion animals because they more accurately re ect tumor characteristics than conventional cell lines and can mimic the tumor microenvironment and cellular interactions through co-culture with nontumor cells.…”

Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids

“…Organoids can thus recapitulate the detailed structure, functions, and features of their original tissues such as self-renewal, organization, and differentiation as well as genetic and molecular imprints ( Lancaster and Knoblich, 2014 ; Elbadawy et al, 2019 ; Elbadawy et al, 2021a ). The recent advances in organoid model revealed substantial promise in biological and translational investigations to evolve recent personalized therapies, particularly for cancer ( Lancaster and Knoblich, 2014 ; Weeber et al, 2017 ; Abugomaa and Elbadawy, 2020 ; Elbadawy et al, 2021b ; Elfadadny et al, 2021 ; Yoshida et al, 2022 ). In a previous article, we generated a new experimental model for MIBC using a dog BC organoid culture ( Elbadawy et al, 2019 ).…”

Evaluation of the efficacy of mitochondrial fission inhibitor (Mdivi-1) using non-alcoholic steatohepatitis (NASH) liver organoids

“…Organoids are 3D cultured tissues made from epithelial cells isolated from organs and can reproduce the cellular composition, structural characteristics, and function of the original tissues at a high level ( Sato et al, 2009 ; Elbadawy et al, 2021a ; Elbadawy et al, 2021b ; Elbadawy et al, 2021c ; Abugomaa et al, 2022 ; Elbadawy et al, 2022 ; Yoshida et al, 2022 ). Compared with traditional 2D cultured cells, the properties of organoids are closer to those of living tissues and organs.…”