Organoids in image-based phenotypic chemical screens

Image-based phenotypic screening relies on the extraction of multivariate information from cells cultured under a large variety of conditions. Technical advances in high-throughput microscopy enable screening in increasingly complex and biologically relevant model systems. To this end, organoids hold great potential for high-content screening because they recapitulate many aspects of parent tissues and can be derived from patient material. However, screening is substantially more difficult in organoids than in classical cell lines from both technical and analytical standpoints. In this review, we present an overview of studies employing organoids for screening applications. We discuss the promises and challenges of small-molecule treatments in organoids and give practical advice on designing, running, and analyzing high-content organoid-based phenotypic screens. Mini-organs: toward successful image-based chemical screening Advances in culture techniques and three-dimensional image analysis algorithms are needed for robust chemical screening of organoids, tiny three-dimensional versions of functioning organs that are derived from stem cells. Organoids can provide useful insights into potential drug targets, cellular behavior, and disease progression, but their complexity provides unique challenges for image-based screening and analyses. Prisca Liberali at the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland, and co-workers reviewed the current status of image-based chemical screening for organoid-based biological and drug research. Careful assay design and process optimization are required, and the volume of generated data can place strain on computational infrastructure. The team highlights the value of multiplexed imaging to improve efficiency, and suggests that neural networks and deep learning may help tackle the complexities of three-dimensional image segmentation analyses.

Automated summary

Image-based phenotypic screening using organoids offers great potential but also unique challenges, requiring careful experimental design and process optimization. Advances in high-throughput microscopy and three-dimensional image analysis algorithms are crucial for robust chemical screening of organoids.