TY - JOUR
KW - Gastrointestinal system
KW - Stem-cell differentiation
KW - Tissue engineering
AU - Holly M. Poling
AU - Théo Noël
AU - Akaljot Singh
AU - Garrett W. Fisher
AU - Konrad Thorner
AU - Praneet Chaturvedi
AU - Kalpana Nattamai
AU - Kalpana Srivastava
AU - Matthew R. Batie
AU - Taylor Hausfeld
AU - Amy L. Pitstick
AU - Nicole E. Brown
AU - Séverine Ménoret
AU - Ignacio Anegon
AU - Riccardo Barrile
AU - Christopher N. Mayhew
AU - Takanori Takebe
AU - James M. Wells
AU - Michael A. Helmrath
AU - Maxime M. Mahe
AB - Key limitations of current human gastrointestinal organoids include incomplete physiological maturation and the need for complex, time-consuming assembloid approaches to integrate a functional nervous system for transplantation. Here we present a confined culture system (CCS) method that generates large-scale, elongated and functional human small intestinal, colonic and gastric tissues with a de novo enteric nervous system (ENS). We use a 3D-printed scaffolding tray to restrict spheroid fusion and growth, promoting the spontaneous co-development of a functional ENS. Transcriptomic and electrophysiological data demonstrate selective neuromuscular function and the presence of excitatory and inhibitory neurons within the tissues. When compared to traditional methods, the CCS expedites tissue maturation for transplantation, yielding organoids that are up to ten times larger, reaching widths of 8 cm after 10 weeks, and exhibit enhanced engraftment rate. CCS organoids integrate and adapt to murine luminal environment while maintaining barrier integrity and functional capacity. The CCS methodology simplifies current protocols while accelerating the production of complex, functional and clinically relevant gut tissues.
BT - Nature Biomedical Engineering
DA - 2026-05-22
DO - 10.1038/s41551-026-01688-6
LA - en
N2 - Key limitations of current human gastrointestinal organoids include incomplete physiological maturation and the need for complex, time-consuming assembloid approaches to integrate a functional nervous system for transplantation. Here we present a confined culture system (CCS) method that generates large-scale, elongated and functional human small intestinal, colonic and gastric tissues with a de novo enteric nervous system (ENS). We use a 3D-printed scaffolding tray to restrict spheroid fusion and growth, promoting the spontaneous co-development of a functional ENS. Transcriptomic and electrophysiological data demonstrate selective neuromuscular function and the presence of excitatory and inhibitory neurons within the tissues. When compared to traditional methods, the CCS expedites tissue maturation for transplantation, yielding organoids that are up to ten times larger, reaching widths of 8 cm after 10 weeks, and exhibit enhanced engraftment rate. CCS organoids integrate and adapt to murine luminal environment while maintaining barrier integrity and functional capacity. The CCS methodology simplifies current protocols while accelerating the production of complex, functional and clinically relevant gut tissues.
PY - 2026
SP - 1
EP - 17
T2 - Nature Biomedical Engineering
TI - Large-scale and innervated functional human gut tissues for transplantation via transient spheroid confinement
UR - https://www.nature.com/articles/s41551-026-01688-6
Y2 - 2026-05-22
SN - 2157-846X
ER -