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

Sugimoto, Seiichiro; Kobayashi, Eiji; Fujii, Mitsuo; Ohta, Yuki; Arai, Kazuya; Matano, Mami; Ishikawa, Kinya; Miyamoto, Kentaro; Toshimitsu, Kohta; Takahashi, Sirirat; Nanki, Kosaku; Hakamata, Yoji; Kanai, Takanori; Sato, Toshiro

doi:10.1038/s41586-021-03247-2

Cited by 75 publications

(110 citation statements)

References 47 publications

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“…Moreover, their recent breakthrough using an organoid-based organ-repurposing approach has expanded culture studies and transplantation procedures [96]. By exploiting the structural similarities between the small intestinal and colonic subepithelia, they have used organoid transplantation to replace colonic epithelium with small intestinal epithelium to generate a "small intestinalized colon" [96]. Using human ileum organoids for xenotransplantation into immunodeficient mice [92], they have shown that the small intestinal organoids rebuild villus structures in the mouse colon [96].…”

Section: Application Of Organoids In Regenerative Medicinementioning

confidence: 99%

“…By exploiting the structural similarities between the small intestinal and colonic subepithelia, they have used organoid transplantation to replace colonic epithelium with small intestinal epithelium to generate a "small intestinalized colon" [96]. Using human ileum organoids for xenotransplantation into immunodeficient mice [92], they have shown that the small intestinal organoids rebuild villus structures in the mouse colon [96]. To understand the spontaneous formation of villus-like structures from xenotransplanted human ileum organoids, they developed a unique 2D culture of small intestinal organoids with continuous flow [96].…”

Section: Application Of Organoids In Regenerative Medicinementioning

confidence: 99%

“…Using human ileum organoids for xenotransplantation into immunodeficient mice [92], they have shown that the small intestinal organoids rebuild villus structures in the mouse colon [96]. To understand the spontaneous formation of villus-like structures from xenotransplanted human ileum organoids, they developed a unique 2D culture of small intestinal organoids with continuous flow [96]. Notably, this mechanical stimulation facilitated the formation of villus-like structures from a monolayer of duodenum and ileum organoids, but not of colon organoids [96].…”

Section: Application Of Organoids In Regenerative Medicinementioning

confidence: 99%

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Modeling Intestinal Stem Cell Function with Organoids

Takahashi

Fujishima

Kengaku

2021

IJMS

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Intestinal epithelial cells (IECs) are crucial for the digestive process and nutrient absorption. The intestinal epithelium is composed of the different cell types of the small intestine (mainly, enterocytes, goblet cells, Paneth cells, enteroendocrine cells, and tuft cells). The small intestine is characterized by the presence of crypt-villus units that are in a state of homeostatic cell turnover. Organoid technology enables an efficient expansion of intestinal epithelial tissue in vitro. Thus, organoids hold great promise for use in medical research and in the development of new treatments. At present, the cholinergic system involved in IECs and intestinal stem cells (ISCs) are attracting a great deal of attention. Thus, understanding the biological processes triggered by epithelial cholinergic activation by acetylcholine (ACh), which is produced and released from neuronal and/or non-neuronal tissue, is of key importance. Cholinergic signaling via ACh receptors plays a pivotal role in IEC growth and differentiation. Here, we discuss current views on neuronal innervation and non-neuronal control of the small intestinal crypts and their impact on ISC proliferation, differentiation, and maintenance. Since technology using intestinal organoid culture systems is advancing, we also outline an organoid-based organ replacement approach for intestinal diseases.

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Section: Application Of Organoids In Regenerative Medicinementioning

confidence: 99%

Section: Application Of Organoids In Regenerative Medicinementioning

confidence: 99%

Section: Application Of Organoids In Regenerative Medicinementioning

confidence: 99%

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Modeling Intestinal Stem Cell Function with Organoids

Takahashi

Fujishima

Kengaku

2021

IJMS

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“…Several platforms being evaluated model mechanical forces normally present in the intestine, including luminal flow and serosal blood flow (shear force) or peristaltic forces [99]. New data suggest that more mature intestinal architecture can be achieved by shaking organoids [100]. Other studies with an intestine-chip model to study E. coli heat-stable enterotoxin signaling suggest fluid flow, and not cyclic stretch, may be the critical mechanophysiologic cue needed for organoid growth and epithelial cell characteristics and infection studies [101].…”

Section: Summary and Current Questionsmentioning

confidence: 99%

Organoids to Dissect Gastrointestinal Virus–Host Interactions: What Have We Learned?

Crawford

Ramani

Blutt

et al. 2021

Viruses

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Historically, knowledge of human host–enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host–microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.

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“…It could be an alternative, before performing an intestinal transplant, which carries a serious risk of severe allogenic reaction. In a new study published in Nature , researchers use organoids to generate a functional small intestinal colon that has potential applications in the treatment of SBS [ 103 , 104 ].…”

Section: Short Bowel Syndrome (And Intestinal Failure)mentioning

confidence: 99%

Small and Large Intestine (II): Inflammatory Bowel Disease, Short Bowel Syndrome, and Malignant Tumors of the Digestive Tract

et al. 2021

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The small intestine is key in the digestion and absorption of macro and micronutrients. The large intestine is essential for the absorption of water, to allow adequate defecation, and to harbor intestinal microbiota, for which their nutritional role is as important as it is unknown. This article will describe the causes and consequences of malnutrition in patients with inflammatory bowel diseases, the importance of screening and replacement of micronutrient deficits, and the main indications for enteral and parenteral nutrition in these patients. We will also discuss the causes of short bowel syndrome, a complex entity due to anatomical or functional loss of part of the small bowel, which can cause insufficient absorption of liquid, electrolytes, and nutrients and lead to complex management. Finally, we will review the causes, consequences, and management of malnutrition in patients with malignant and benign digestive tumors, including neuroendocrine tumors (present not only in the intestine but also in the pancreas).

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

Cited by 75 publications

References 47 publications

Modeling Intestinal Stem Cell Function with Organoids

Modeling Intestinal Stem Cell Function with Organoids

Organoids to Dissect Gastrointestinal Virus–Host Interactions: What Have We Learned?

Small and Large Intestine (II): Inflammatory Bowel Disease, Short Bowel Syndrome, and Malignant Tumors of the Digestive Tract

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