@article{bibcite_4001, keywords = {Bioengineering, Colon, colonocyte, gastrointestinal drug toxicity, gut physiology, mucus, organ-on-chip, organoid, small intestine}, author = {Olga Mitrofanova and Mikhail Nikolaev and Quan Xu and Nicolas Broguiere and Irineja Cubela and J. Gray Camp and Michael Bscheider and Matthias P. Lutolf}, title = {Bioengineered human colon organoids with in~vivo-like cellular complexity and function}, abstract = {Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease in~vitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling in~vivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called {\textquotedblleft}mini-colons.{\textquotedblright} By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated in~vivo-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.}, year = {2024}, journal = {Cell Stem Cell}, volume = {31}, pages = {1175-1186.e7}, month = {2024-08-01}, issn = {1934-5909}, url = {https://www.sciencedirect.com/science/article/pii/S193459092400184X}, doi = {10.1016/j.stem.2024.05.007}, }