Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Gastrointestinal toxicity (GI-tox) is a common clinical adverse event. It is very important to clarify GI-tox concerns in the nonclinical stage because of reduction of patients' QOL.
Monolayer culture of single cell line has been the main method to evaluate GI-tox in vitro. These methods are impossible to detect the effects on stem cells or interactions between cells, and therefore have poor detection sensitivity, reproducibility and predictivity for clinical GI-tox. Intestinal organoids have a three-dimensional structure including undifferentiated cells, thus GI-tox can be evaluated in a closer environment to the body. However, assays using complex in vitro model such as organoids are often difficult to operate. Therefore, it is necessary to develop a new evaluation system for GI-tox with high accuracy and throughput.
We found that GI-tox induced compounds reduced organoids size. Therefore, we considered evaluating GI-tox by organoids size quantification. Then, we developed an application that can recognize organoids from bright-field images and extract feature values. The size of intestinal organoids was to be a sensitive marker to detect GI-tox. Furthermore, this application is superior in convenience because analysis can be performed only using bright-field images, leading to a reduction in the burden on experimenters.
In this presentation, we will introduce the developed organoid image analysis application and the GI-tox evaluation system, and discuss the future development in nonclinical safety evaluation.
