TY - JOUR
KW - Bioengineering
KW - Colon
KW - colonocyte
KW - gastrointestinal drug toxicity
KW - gut physiology
KW - mucus
KW - organ-on-chip
KW - organoid
KW - small intestine
AU - Olga Mitrofanova
AU - Mikhail Nikolaev
AU - Quan Xu
AU - Nicolas Broguiere
AU - Irineja Cubela
AU - J. Gray Camp
AU - Michael Bscheider
AU - Matthias P. Lutolf
AB - 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 “mini-colons.” 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.
BT - Cell Stem Cell
DA - 2024-08-01
DO - 10.1016/j.stem.2024.05.007
IS - 8
N2 - 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 “mini-colons.” 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.
PY - 2024
SP - 1175
EP - 1186.e7
T2 - Cell Stem Cell
TI - Bioengineered human colon organoids with in vivo-like cellular complexity and function
UR - https://www.sciencedirect.com/science/article/pii/S193459092400184X
VL - 31
Y2 - 2024-08-13
SN - 1934-5909
ER -