Intestinal organoids have thus far been among the gut organoids generated directly from intestinal tissues or pluripotent stem cells. One way human pluripotent stem cells can be driven to form intestinal organoids is through first the application of activin A to drive the cells into a mesoendodermal identity, followed by the pharmacological upregulation of Wnt3a and Fgf4 signaling pathways as they have been demonstrated to promote posterior gut fate. Intestinal organoids have also been generated from intestinal stem cells, extracted from adult tissue and cultured in 3D media. These adult stem cell-derived organoids are often referred to as enteroids or colonoids, depending on their segment of origin, and have been established from both the human and murine intestine. Intestinal organoids consist of a single layer of polarized intestinal epithelial cells surrounding a central lumen. As such, recapitulate the crypt-villus structure of the intestine, by recapitulating its function, physiology and organization, and maintaining all the cell types found normally in the structure including intestinal stem cells. Thus, intestinal organoids are a valuable model to study intestinal nutrient transport, drug absorption and delivery, nanomaterials and nanomedicine, incretin hormone secretion, and infection by various enteropathogens. For example, Qun Wang's team rationally designed artificial virus nanoparticles as oral drug delivery vehicles (ODDVs) with gut organoid-derived mucosal models and demonstrated a new concept of using newly established colon organoids as tools for high-throughput drug screening, toxicity testing, and oral drug development. Intestinal organoids also recapitulate the crypt-Villus structure to such a high degree of fidelity that they have been successfully transplanted to mouse intestines, and are hence highly regarded as a valuable model for research. One of the fields of research that intestinal organoids have been utilized is that of stem cell niche. Intestinal organoids were used to study the nature of the intestinal stem cell niche, and research done with them demonstrated the positive role IL-22 has in maintaining in intestinal stem cells, along with demonstrating the roles of other cell types like neurons and fibroblasts in maintenance of intestinal stem cells. In the field of infection biology, different intestinal organoid-based model systems have been explored. On one hand, organoids can be infected in bulk by simply mixing them with the enteropathogen of interest. However, to model infection via a more natural route starting from the intestinal lumen, microinjection of the pathogen is required. In addition, the polarity of intestinal organoids can be inverted, and they can even be dissociated into single cells and cultured as 2D monolayers in order to make both the apical and basolateral sides of the epithelium more easily accessible. Intestinal organoids have also demonstrated therapeutic potential.
In order to more accurately recapitulate the intestine in vivo, co-cultures of intestinal organoids and immune cells have been developed. Furthermore, organ-on-a-chip models combine intestinal organoids with other cell types such as endothelial or immune cells as well as peristaltic flow.