Author
Listed:
- Shinya Sugimoto
(Keio University School of Medicine
Keio University School of Medicine)
- Eiji Kobayashi
(Keio University School of Medicine)
- Masayuki Fujii
(Keio University School of Medicine
The University of Tokyo)
- Yuki Ohta
(Keio University School of Medicine)
- Kazuya Arai
(Keio University School of Medicine
JSR Corporation)
- Mami Matano
(Keio University School of Medicine)
- Keiko Ishikawa
(Keio University School of Medicine
Keio University School of Medicine)
- Kentaro Miyamoto
(Keio University School of Medicine
Miyarisan Pharmaceutical Co. Ltd)
- Kohta Toshimitsu
(Keio University School of Medicine
Keio University School of Medicine)
- Sirirat Takahashi
(Keio University School of Medicine)
- Kosaku Nanki
(Keio University School of Medicine
Keio University School of Medicine)
- Yoji Hakamata
(Nippon Veterinary and Life Science University
Nippon Veterinary and Life Science University)
- Takanori Kanai
(Keio University School of Medicine)
- Toshiro Sato
(Keio University School of Medicine
Keio University School of Medicine)
Abstract
The small intestine is the main organ for nutrient absorption, and its extensive resection leads to malabsorption and wasting conditions referred to as short bowel syndrome (SBS). Organoid technology enables an efficient expansion of intestinal epithelium tissue in vitro1, but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging2. Here we generate a functional small intestinalized colon (SIC) by replacing the native colonic epithelium with ileum-derived organoids. We first find that xenotransplanted human ileum organoids maintain their regional identity and form nascent villus structures in the mouse colon. In vitro culture of an organoid monolayer further reveals an essential role for luminal mechanistic flow in the formation of villi. We then develop a rat SIC model by repositioning the SIC at the ileocaecal junction, where the epithelium is exposed to a constant luminal stream of intestinal juice. This anatomical relocation provides the SIC with organ structures of the small intestine, including intact vasculature and innervation, villous structures, and the lacteal (a fat-absorbing lymphatic structure specific to the small intestine). The SIC has absorptive functions and markedly ameliorates intestinal failure in a rat model of SBS, whereas transplantation of colon organoids instead of ileum organoids invariably leads to mortality. These data provide a proof of principle for the use of intestinal organoids for regenerative purposes, and offer a feasible strategy for SBS treatment.
Suggested Citation
Shinya Sugimoto & Eiji Kobayashi & Masayuki Fujii & Yuki Ohta & Kazuya Arai & Mami Matano & Keiko Ishikawa & Kentaro Miyamoto & Kohta Toshimitsu & Sirirat Takahashi & Kosaku Nanki & Yoji Hakamata & Ta, 2021.
"An organoid-based organ-repurposing approach to treat short bowel syndrome,"
Nature, Nature, vol. 592(7852), pages 99-104, April.
Handle:
RePEc:nat:nature:v:592:y:2021:i:7852:d:10.1038_s41586-021-03247-2
DOI: 10.1038/s41586-021-03247-2
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Citations
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Cited by:
- Ohman Kwon & Hana Lee & Jaeeun Jung & Ye Seul Son & Sojeong Jeon & Won Dong Yoo & Naeun Son & Kwang Bo Jung & Eunho Choi & In-Chul Lee & Hyung-Jun Kwon & Chuna Kim & Mi-Ok Lee & Hyun-Soo Cho & Dae Soo, 2024.
"Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids,"
Nature Communications, Nature, vol. 15(1), pages 1-14, December.
- Fang-Ling Zhang & Zhen Hu & Yi-Fan Wang & Wen-Juan Zhang & Bo-Wei Zhou & Qi-Shun Sun & Ze-Bin Lin & Ke-Xuan Liu, 2023.
"Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization,"
Nature Communications, Nature, vol. 14(1), pages 1-19, December.
- Maame Efua S. Sampah & Hannah Moore & Raheel Ahmad & Johannes Duess & Peng Lu & Carla Lopez & Steve Steinway & Daniel Scheese & Zachariah Raouf & Koichi Tsuboi & Jeffrey Ding & Connor Caputo & Madison, 2024.
"Xenotransplanted human organoids identify transepithelial zinc transport as a key mediator of intestinal adaptation,"
Nature Communications, Nature, vol. 15(1), pages 1-16, December.
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