An organoid-based organ-repurposing approach to treat short bowel syndrome
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 vitro 1 , but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging 2 . 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…
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Intestinal organoids can fuse into tubular structures resembling in vivo intestines.
“Sachs and colleagues showed that intestinal organoids could fuse into tubular structures resembling in vivo intestines148,149.”
From Organoids (2022) · cites this paper as [148]
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- Authors
- Sugimoto, S., Kobayashi, E., Fujii, M., Ohta, Y., Arai, K., Matano, M., Ishikawa, K., Miyamoto, K., Toshimitsu, K., Takahashi, S., Nanki, K., Hakamata, Y., Kanai, T., & Sato, T.
- Affiliations
- Keio University (JP)
- Nippon Veterinary and Life Science University (JP)
- Corresponding author
- Kobayashi, Eiji
- Sato, Toshiro
- ORCID
- Venue
- Nature
- Published
- 2021-02-24
- Volume
- 592
- Issue
- 7852
- Pages
- 99-104
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3133476978
- Cited by
- 175
- References
- 48
- Citations by year
- 2026: 27 · 2025: 24 · 2024: 37 · 2023: 30 · 2022: 40 · 2021: 17
- FWCI
- 29.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (20H03746, 23K20316, 17H06176, 20H03757)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Keywords
- short bowel syndrome, intestinal organoids, organoid transplantation, intestinal failure, villus formation, luminal flow, intestinal regeneration, lacteals, intestinal epithelium, xenotransplantation, rat model
- MeSH terms
- Animals, Colon, Disease Models, Animal, Humans, Ileum, Intestinal Mucosa, Male, Organ Culture Techniques, Organoids, Rats, Inbred Lew, Regeneration, Short Bowel Syndrome, Regenerative Medicine, Rats, Heterografts
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