Tissue geometry drives deterministic organoid patterning.

Epithelial organoids are stem cell­derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.

Extracellular matrix requirements for gastrointestinal organoid cultures.

Organoids are a new class of biological model systems that have garnered significant interest in the life sciences. When provided with the proper 3D matrix and biochemical factors, stem cells can self-organize and form tissue-specific organoids. Thus far, there has been a substantial effort to identify soluble niche components essential for organoid culture; however, the role of the solid extracellular matrix (ECM) as an essential element of the niche is still largely lacking. In this review, we discuss the importance of the ECM in intestinal, hepatic, and pancreatic organoid culture and how biomaterial-based approaches can be used to probe different ECM properties required for more physiologically and translationally relevant organoid models.