Homeostatic mini-intestines through scaffold-guided organoid morphogenesis.

Details

Serval ID
serval:BIB_E75958C4FC02
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Homeostatic mini-intestines through scaffold-guided organoid morphogenesis.
Journal
Nature
Author(s)
Nikolaev M., Mitrofanova O., Broguiere N., Geraldo S., Dutta D., Tabata Y., Elci B., Brandenberg N., Kolotuev I., Gjorevski N., Clevers H., Lutolf M.P.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
09/2020
Peer-reviewed
Oui
Volume
585
Number
7826
Pages
574-578
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology <sup>1-4</sup> . However, the approaches that are used at present to derive these organoids in three-dimensional matrices <sup>5,6</sup> result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation and prohibits homeostasis. Here, by using tissue engineering and the intrinsic self-organization properties of cells, we induce intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host-microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our 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.
Keywords
Animals, Body Patterning, Cell Differentiation, Cell Lineage, Cryptosporidium parvum/pathogenicity, Homeostasis, Human Embryonic Stem Cells/cytology, Human Umbilical Vein Endothelial Cells, Humans, Intestines/cytology, Intestines/embryology, Intestines/parasitology, Intestines/pathology, Mice, Models, Biological, Morphogenesis, Organoids/cytology, Organoids/embryology, Organoids/parasitology, Organoids/pathology, Regeneration, Regenerative Medicine, Stem Cells, Tissue Culture Techniques/methods, Tissue Engineering, Tissue Scaffolds
Pubmed
Web of science
Create date
28/09/2020 12:30
Last modification date
29/07/2022 5:38
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