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Intestinal organoids in infants and children

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Abstract

Recent advances in culturing of intestinal stem cells and pluripotent stem cells have led to the development of intestinal organoids. These are self-organizing 3D structures, which recapitulate the characteristics and physiological features of in vivo intestinal epithelium. Intestinal organoids have allowed the development of novel in vitro models to study various gastrointestinal diseases expanding our understanding of the pathophysiology of diseases and leading to the development of innovative therapies. This article aims to summarize the current usage of intestinal organoids as a model of gastrointestinal diseases and the potential applications of intestinal organoids in infants and children. Intestinal organoids allow the study of intestinal epithelium responses to stress factors. Mimicking intestinal injury such as necrotizing enterocolitis, intestinal organoids increases the expression of pro-inflammatory cytokine genes and shows disruption of tight junctions after they are injured by lipopolysaccharide and hypoxia. In cystic fibrosis, intestinal organoids derived from rectal biopsies have provided benefits in genetic studies and development of novel therapeutic gene modulation. Transplantation of intestinal organoids via enema has been shown to rescue damaged colonic epithelium in mice. In addition, tissue-engineered small intestine derived from intestinal organoids have been successfully established providing a potential novel treatment and a new hope for children with short bowel syndrome.

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Abbreviations

PSCs:

Pluripotent stem cells

ASCs:

Adult stem cells

Lgr5:

Leucine-rich repeat containing G-protein-coupled receptor 5

NEC:

Necrotizing enterocolitis

HIOs:

Human intestinal organoids

TESI:

Tissue-engineered small intestine

ENCCs:

Enteric neural crest cells

CFTR:

Cystic transmembrane conductance regulator

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Acknowledgements

Prof. Agostino Pierro was supported by the Canadian Institutes of Health Research (CIHR) Foundation Grant (#353857) and the Robert M. Filler Chair of Surgery, The Hospital for Sick Children.

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Authors and Affiliations

  1. Division of Pediatric Surgery, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

    Sinobol Chusilp

  2. Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, University of Toronto, 1526-555 University Ave, Toronto, ON, M5G 1X8, Canada

    Sinobol Chusilp, Bo Li, Dorothy Lee, Carol Lee & Agostino Pierro

  3. Division of Pediatric Surgery, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Paisarn Vejchapipat

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  1. Sinobol Chusilp
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  2. Bo Li
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Chusilp, S., Li, B., Lee, D. et al. Intestinal organoids in infants and children. Pediatr Surg Int 36, 1–10 (2020). https://doi.org/10.1007/s00383-019-04581-3

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