PSC-derived intestinal organoids with apical-out orientation as a tool to study nutrient uptake, drug absorption and metabolism.

Intestinal organoids recapitulate many features of the gastrointestinal tract and have revolutionized studies of intestinal function and disease. However, the restricted accessibility of the apical surface of the organoids facing the central lumen (apical-in) limits studies related to nutrient uptake and drug absorption and metabolism. Here, we demonstrate that pluripotent stem cell (PSC)-derived intestinal organoids with reversed epithelial polarity (apical-out) can successfully recapitulate tissue-specific functions.

Hypoxia-tolerant apical-out intestinal organoids to model host-microbiome interactions.

Microbiome is an integral part of the gut and is essential for its proper function. Imbalances of the microbiota can be devastating and have been linked with several gastrointestinal conditions. Current gastrointestinal models do not fully reflect the in vivo situation.

A Microwell-Based Intestinal Organoid-Macrophage Co-Culture System to Study Intestinal Inflammation.

The mammalian intestinal epithelium contains more immune cells than any other tissue, and this is largely because of its constant exposure to pathogens. Macrophages are crucial for maintaining intestinal homeostasis, but they also play a central role in chronic pathologies of the digestive system. We developed a versatile microwell-based intestinal organoid-macrophage co-culture system that enables us to recapitulate features of intestinal inflammation.

Reversing Epithelial Polarity in Pluripotent Stem Cell-Derived Intestinal Organoids.

The inner surface of the intestine is a dynamic system, composed of a single layer of polarized epithelial cells. The development of intestinal organoids was a major breakthrough since they robustly recapitulate intestinal architecture, regional specification and cell composition . However, the cyst-like organization hinders direct access to the apical side of the epithelium, thus limiting their use in functional assays.

Challenges to, and prospects for, reverse engineering the gastrointestinal tract using organoids.

For over a decade, organoids mimicking the development, physiology, and disease of the digestive system have been a topic of broad interest and intense study. Establishing organoid models that recapitulate all distinct regions of the gastrointestinal tract (GIT) has proven challenging since each tissue surrogate requires tailor-made modifications of the original protocol to generate intestinal organoids. In this review, we discuss the challenges and current advances of the GIT organoid models.

Intestinal Organoid Culture in Polymer Film-Based Microwell Arrays.

As organoids offer a promising tool to study cell biology and model diseases, organoid technology has rapidly evolved over the last few years. Even though intestinal organoids are one of the most well-established organoid systems, they currently rely on the embedding into an excess amount of poorly defined, tumor-derived extracellular matrix. Here, a novel suspension method is suggested to grow mouse intestinal organoids inside thermoformed microwell arrays.