An organoid-based organ-repurposing approach to treat short bowel syndrome

Shinya Sugimoto, Eiji Kobayashi (), Masayuki Fujii, Yuki Ohta, Kazuya Arai, Mami Matano, Keiko Ishikawa, Kentaro Miyamoto, Kohta Toshimitsu, Sirirat Takahashi, Kosaku Nanki, Yoji Hakamata, Takanori Kanai and Toshiro Sato ()
Additional contact information
Shinya Sugimoto: Keio University School of Medicine
Eiji Kobayashi: Keio University School of Medicine
Masayuki Fujii: Keio University School of Medicine
Yuki Ohta: Keio University School of Medicine
Kazuya Arai: Keio University School of Medicine
Mami Matano: Keio University School of Medicine
Keiko Ishikawa: Keio University School of Medicine
Kentaro Miyamoto: Keio University School of Medicine
Kohta Toshimitsu: Keio University School of Medicine
Sirirat Takahashi: Keio University School of Medicine
Kosaku Nanki: Keio University School of Medicine
Yoji Hakamata: Nippon Veterinary and Life Science University
Takanori Kanai: Keio University School of Medicine
Toshiro Sato: Keio University School of Medicine

Nature, 2021, vol. 592, issue 7852, 99-104

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03247-2 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:592:y:2021:i:7852:d:10.1038_s41586-021-03247-2

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03247-2

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().