TY - JOUR
KW - Humans
KW - Inflammatory Bowel Diseases
KW - Intestines
KW - Organogenesis
KW - organoids
KW - Stem cells
AU - Sunghee Estelle Park
AU - Shawn Kang
AU - Jungwook Paek
AU - Andrei Georgescu
AU - Jeehan Chang
AU - Alex Yoon Yi
AU - Benjamin J. Wilkins
AU - Tatiana A. Karakasheva
AU - Kathryn E. Hamilton
AU - Dan Dongeun Huh
AB - Here, we introduce a facile, scalable engineering approach to enable long-term development and maturation of organoids. We have redesigned the configuration of conventional organoid culture to develop a platform that converts single injections of stem cell suspensions to radial arrays of organoids that can be maintained for extended periods without the need for passaging. Using this system, we demonstrate accelerated production of intestinal organoids with significantly enhanced structural and functional maturity, and their continuous development for over 4 weeks. Furthermore, we present a patient-derived organoid model of inflammatory bowel disease (IBD) and its interrogation using single-cell RNA sequencing to demonstrate its ability to reproduce key pathological features of IBD. Finally, we describe the extension of our approach to engineer vascularized, perfusable human enteroids, which can be used to model innate immune responses in IBD. This work provides an immediately deployable platform technology toward engineering more realistic organ-like structures in a dish.
BT - Nature Methods
DA - 2022-11
DO - 10.1038/s41592-022-01643-8
IS - 11
LA - eng
N2 - Here, we introduce a facile, scalable engineering approach to enable long-term development and maturation of organoids. We have redesigned the configuration of conventional organoid culture to develop a platform that converts single injections of stem cell suspensions to radial arrays of organoids that can be maintained for extended periods without the need for passaging. Using this system, we demonstrate accelerated production of intestinal organoids with significantly enhanced structural and functional maturity, and their continuous development for over 4 weeks. Furthermore, we present a patient-derived organoid model of inflammatory bowel disease (IBD) and its interrogation using single-cell RNA sequencing to demonstrate its ability to reproduce key pathological features of IBD. Finally, we describe the extension of our approach to engineer vascularized, perfusable human enteroids, which can be used to model innate immune responses in IBD. This work provides an immediately deployable platform technology toward engineering more realistic organ-like structures in a dish.
PY - 2022
SP - 1449
EP - 1460
T2 - Nature Methods
TI - Geometric engineering of organoid culture for enhanced organogenesis in a dish
VL - 19
SN - 1548-7105
ER -