Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications

  title={Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications},
  author={Toshiro Sato and Hans Clevers},
  pages={1190 - 1194}
Recent examples have highlighted how stem cells have the capability to initiate morphogenesis in vitro; that is, to generate complex structures in culture that closely parallel their in vivo counterparts. Lgr5, the receptor for the Wnt-agonistic R-spondins, marks stem cells in multiple adult organs of mice and humans. In R-spondin–based three-dimensional cultures, these Lgr5 stem cells can grow into ever-expanding epithelial organoids that retain their original organ identity. Single Lgr5 stem… 

Mini-gut organoids: reconstitution of the stem cell niche.

The mechanism of self-renewal in organoids provides novel insights for organogenesis, regenerative medicine, and tumorigenesis of the digestive system.

Ex vivo culture of the intestinal epithelium: strategies and applications

Novel genome-editing techniques have been successfully employed to functionally repair disease loci in cultured intestinal stem cells from human patients with a hereditary defect, and it is anticipated that this technology will be instrumental in exploiting the regenerative medicine potential of human intestine stem cells for treating human disorders in the intestinal tract and for creating near-physiological ex vivo models of human gastrointestinal disease.

Homeostatic mini-intestines through scaffold-guided organoid morphogenesis

The concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions.

Novel approaches: Tissue engineering and stem cells--In vitro modelling of the gut.

Intestinal epithelial organoids fuse to form self-organizing tubes in floating collagen gels

The remarkable self-organizing properties of Lgr5+ stem cells extend beyond the level of the microscopic cystic organoid to the next, macroscopic, level of tube formation.

Monolayer culture of intestinal epithelium sustains Lgr5+ intestinal stem cells

A bona fide 2D monolayer culture system to study Lgr5 ISCs and facilitate drug screening is established and the addition of blebbistatin greatly enhanced the attachment and growth of intestinal epithelial cells on Matrigel-coated plate.

A Development-Inspired Niche for Homeostatic Human Mini-Intestines

Epithelial organoids derived from intestinal tissue, also referred to as mini-intestines or mini-guts, recapitulate many aspects of the organ in vitro and can be used for biological discovery,

Organoids and Their Use in Modeling Gut Epithelial Cell Lineage Differentiation and Barrier Properties During Intestinal Diseases

The different origins and recent use of organoids in modeling intestinal epithelial differentiation and barrier properties are summarized.

Reversing Epithelial Polarity in Pluripotent Stem Cell-Derived Intestinal Organoids

This novel model lays the foundation for developing new in vitro functional assays particularly targeting the apical surface of the epithelium and thus offers a new research tool to study nutrient/drug uptake, metabolism and host-microbiome/pathogen interactions.

Current knowledge on the multiform reconstitution of intestinal stem cell niche

The recent advances in the microfabrication of intestinal organoids on hydrogel systems are reviewed to contribute to multiform reconstitution of the ISC niche.



Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche

It is concluded that intestinal crypt–villus units are self-organizing structures, which can be built from a single stem cell in the absence of a non-epithelial cellular niche.

Stem cells, self-renewal, and differentiation in the intestinal epithelium.

In this review, the identification of intestinal stem cells is described and genetic studies that have helped to elucidate those signals important for progenitor cells to differentiate into one of the specialized intestinal epithelial cell types are discussed.

Paneth Cells in Intestinal Homeostasis and Tissue Injury

Small intestinal label-retaining cells (LRCs) persisting in the lower third of the crypt of Lieberkühn for up to 100 days are isolated and characterized and are likely to contribute to the regenerative process following tissue insults such as chronic inflammation.

Intestinal label-retaining cells are secretory precursors expressing Lgr5

The rapid cell turnover of the intestinal epithelium is achieved from small numbers of stem cells located in the base of glandular crypts. These stem cells have been variously described as rapidly

Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas

Studying mouse models, direct, functional evidence is provided for the presence of stem cell activity within primary intestinal adenomas, a precursor to intestinal cancer.

Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell

Methods for long-term expansion of colonic stem cells positive for leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5+ cells) in culture are described, showing the feasibility of colon stem-cell therapy based on the in vitro expansion of a single adult Colonic stem cell.

Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts

It is concluded that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell, in colon crypts, and co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation.

Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche

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Identification of stem cells in small intestine and colon by marker gene Lgr5

The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers, suggesting that it represents the stem cell of the small intestine and colon.

Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells

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