Evaluating Compound Toxicity Effects On Healthy Intestinal Organoids Using High-Content Imaging

By Oksana Sirenko and Krishna Macha, Molecular Devices

This content is brought to you by Molecular Devices, a Danaher Operating Company.

Many drugs fail in the later stages of the drug development pipeline due to unacceptable toxicity effects. These failures in clinical trials are often attributed to insufficient predictive models used to screen drug candidates. Three-dimensional (3D) organoids show promise in enhancing the predictivity of in vitro assays and underscore the value of incorporating organoids in pre-clinical testing.

One of the most common side effects of anti-cancer drugs is their toxicity to the intestine, which frequently limits the dosage that can be safely administered to patients. In vitro assays utilizing 3D organoids can effectively evaluate the toxic effects of anti-cancer compounds to provide crucial information during the drug development process. The use of automated high-content imaging significantly increases throughput and broadens the scope of information regarding toxicity effects, particularly in relation to complex 3D biological models.

Examine a method developed to assess toxicity using 3D mouse intestinal organoids cultured in Matrigel domes, where concentration-dependent phenotypic effects of 10 different compounds were tested.