In-silicoandin-vitromorphometric analysis of intestinal organoids

Autor: Sandra Montes-Olivas, Danny Legge, Abbie Lund, Alexander G. Fletcher, Ann C. Williams, Lucia Marucci, Martin Homer
Rok vydání: 2022
Popis: Organoids offer a powerful model to study cellular self-organisation, the growth of specific tissue morphologiesin-vitro, and to assess potential medical therapies. However, the intrinsic mechanisms of these systems are not entirely understood yet, which can result in variability of organoids due to differences in culture conditions and basement membrane extracts used. Improving the standardisation of organoid cultures is essential for their implementation in clinical protocols. Developing tools to assess and predict the behaviour of these systems may produce a more robust and standardised biological model to perform accurate clinical studies. Here we developed an algorithm to automate crypt-like structure counting on intestinal organoids in bothin-vitroandin-silicoimages. In addition, we modified an existing two-dimensional agent-based mathematical model of intestinal organoids to better describe the system physiology, and evaluated its ability to replicate budding structures compared to new experimental data we generated. The crypt-counting algorithm proved useful in approximating the average budding structures found in ourin-vitrointestinal organoid culture images on days 3 and 7 after seeding. Our changes to thein-silicomodel maintain the potential to produce simulations that replicate the number of budding structures found on days 5 and 7 ofin-vitrodata. The present study aims to aid in quantifying key morphological structures and provide a method to compare bothin-vitroandin-silicoexperiments. Our results could be extended later to 3Din-silicomodels.
Databáze: OpenAIRE