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An organoid-based organ-repurposing approach to treat short bowel syndrome
by
Ishikawa, Keiko
, Sugimoto, Shinya
, Miyamoto, Kentaro
, Nanki, Kosaku
, Kanai, Takanori
, Ohta, Yuki
, Takahashi, Sirirat
, Hakamata, Yoji
, Fujii, Masayuki
, Kobayashi, Eiji
, Arai, Kazuya
, Toshimitsu, Kohta
, Matano, Mami
, Sato, Toshiro
in
101/1
/ 119/118
/ 59
/ 631/532/2437
/ 64
/ 692/308/2171
/ 692/699/1503/1702/295
/ 82/1
/ 82/80
/ 82/83
/ 9/10
/ 96
/ Absorption
/ Absorptivity
/ Animals
/ Cholesterol
/ Colon
/ Colon - blood supply
/ Colon - cytology
/ Colon - innervation
/ Colon - surgery
/ Disease Models, Animal
/ Epithelium
/ Heterografts
/ Humanities and Social Sciences
/ Humans
/ Ileum
/ Ileum - cytology
/ Ileum - transplantation
/ Innervation
/ Intestinal Mucosa - blood supply
/ Intestinal Mucosa - cytology
/ Intestinal Mucosa - innervation
/ Intestinal Mucosa - surgery
/ Intestine
/ Malabsorption
/ Male
/ Microscopy
/ multidisciplinary
/ Organ Culture Techniques
/ Organoids
/ Organoids - cytology
/ Organoids - transplantation
/ Rats
/ Rats, Inbred Lew
/ Regeneration
/ Regenerative Medicine - methods
/ Relocation
/ Science
/ Science (multidisciplinary)
/ Short bowel syndrome
/ Short Bowel Syndrome - pathology
/ Short Bowel Syndrome - surgery
/ Short Bowel Syndrome - therapy
/ Small intestine
/ Transplantation
/ Villus
/ Xenografts
2021
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An organoid-based organ-repurposing approach to treat short bowel syndrome
by
Ishikawa, Keiko
, Sugimoto, Shinya
, Miyamoto, Kentaro
, Nanki, Kosaku
, Kanai, Takanori
, Ohta, Yuki
, Takahashi, Sirirat
, Hakamata, Yoji
, Fujii, Masayuki
, Kobayashi, Eiji
, Arai, Kazuya
, Toshimitsu, Kohta
, Matano, Mami
, Sato, Toshiro
in
101/1
/ 119/118
/ 59
/ 631/532/2437
/ 64
/ 692/308/2171
/ 692/699/1503/1702/295
/ 82/1
/ 82/80
/ 82/83
/ 9/10
/ 96
/ Absorption
/ Absorptivity
/ Animals
/ Cholesterol
/ Colon
/ Colon - blood supply
/ Colon - cytology
/ Colon - innervation
/ Colon - surgery
/ Disease Models, Animal
/ Epithelium
/ Heterografts
/ Humanities and Social Sciences
/ Humans
/ Ileum
/ Ileum - cytology
/ Ileum - transplantation
/ Innervation
/ Intestinal Mucosa - blood supply
/ Intestinal Mucosa - cytology
/ Intestinal Mucosa - innervation
/ Intestinal Mucosa - surgery
/ Intestine
/ Malabsorption
/ Male
/ Microscopy
/ multidisciplinary
/ Organ Culture Techniques
/ Organoids
/ Organoids - cytology
/ Organoids - transplantation
/ Rats
/ Rats, Inbred Lew
/ Regeneration
/ Regenerative Medicine - methods
/ Relocation
/ Science
/ Science (multidisciplinary)
/ Short bowel syndrome
/ Short Bowel Syndrome - pathology
/ Short Bowel Syndrome - surgery
/ Short Bowel Syndrome - therapy
/ Small intestine
/ Transplantation
/ Villus
/ Xenografts
2021
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An organoid-based organ-repurposing approach to treat short bowel syndrome
by
Ishikawa, Keiko
, Sugimoto, Shinya
, Miyamoto, Kentaro
, Nanki, Kosaku
, Kanai, Takanori
, Ohta, Yuki
, Takahashi, Sirirat
, Hakamata, Yoji
, Fujii, Masayuki
, Kobayashi, Eiji
, Arai, Kazuya
, Toshimitsu, Kohta
, Matano, Mami
, Sato, Toshiro
in
101/1
/ 119/118
/ 59
/ 631/532/2437
/ 64
/ 692/308/2171
/ 692/699/1503/1702/295
/ 82/1
/ 82/80
/ 82/83
/ 9/10
/ 96
/ Absorption
/ Absorptivity
/ Animals
/ Cholesterol
/ Colon
/ Colon - blood supply
/ Colon - cytology
/ Colon - innervation
/ Colon - surgery
/ Disease Models, Animal
/ Epithelium
/ Heterografts
/ Humanities and Social Sciences
/ Humans
/ Ileum
/ Ileum - cytology
/ Ileum - transplantation
/ Innervation
/ Intestinal Mucosa - blood supply
/ Intestinal Mucosa - cytology
/ Intestinal Mucosa - innervation
/ Intestinal Mucosa - surgery
/ Intestine
/ Malabsorption
/ Male
/ Microscopy
/ multidisciplinary
/ Organ Culture Techniques
/ Organoids
/ Organoids - cytology
/ Organoids - transplantation
/ Rats
/ Rats, Inbred Lew
/ Regeneration
/ Regenerative Medicine - methods
/ Relocation
/ Science
/ Science (multidisciplinary)
/ Short bowel syndrome
/ Short Bowel Syndrome - pathology
/ Short Bowel Syndrome - surgery
/ Short Bowel Syndrome - therapy
/ Small intestine
/ Transplantation
/ Villus
/ Xenografts
2021
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An organoid-based organ-repurposing approach to treat short bowel syndrome
Journal Article
An organoid-based organ-repurposing approach to treat short bowel syndrome
2021
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Overview
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 for regenerative purposes, and offer a feasible strategy for SBS treatment.
In a rat model of short bowel syndrome, transplantation of small intestinal organoids into the colon partially restores intestinal function and improves survival—a proof of principle that organoid transplantation might have therapeutic benefit.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 119/118
/ 59
/ 64
/ 82/1
/ 82/80
/ 82/83
/ 9/10
/ 96
/ Animals
/ Colon
/ Humanities and Social Sciences
/ Humans
/ Ileum
/ Intestinal Mucosa - blood supply
/ Intestinal Mucosa - cytology
/ Intestinal Mucosa - innervation
/ Male
/ Rats
/ Regenerative Medicine - methods
/ Science
/ Short Bowel Syndrome - pathology
/ Short Bowel Syndrome - surgery
/ Short Bowel Syndrome - therapy
/ Villus
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