Homeostatic mini-intestines through scaffold-guided organoid morphogenesis
Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology1-4. However, the approaches that are used at present to derive these organoids in three-dimensional matrices5,6 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.
Errataetall: |
CommentIn: Nat Rev Gastroenterol Hepatol. 2020 Nov;17(11):649. - PMID 32994569 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:585 |
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Enthalten in: |
Nature - 585(2020), 7826 vom: 16. Sept., Seite 574-578 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Nikolaev, Mikhail [VerfasserIn] |
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Date Completed 26.10.2020 Date Revised 11.05.2021 published: Print-Electronic CommentIn: Nat Rev Gastroenterol Hepatol. 2020 Nov;17(11):649. - PMID 32994569 Citation Status MEDLINE |
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doi: |
10.1038/s41586-020-2724-8 |
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funding: |
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PPN (Katalog-ID): |
NLM31510645X |
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500 | |a Citation Status MEDLINE | ||
520 | |a Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology1-4. However, the approaches that are used at present to derive these organoids in three-dimensional matrices5,6 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
700 | 1 | |a Mitrofanova, Olga |e verfasserin |4 aut | |
700 | 1 | |a Broguiere, Nicolas |e verfasserin |4 aut | |
700 | 1 | |a Geraldo, Sara |e verfasserin |4 aut | |
700 | 1 | |a Dutta, Devanjali |e verfasserin |4 aut | |
700 | 1 | |a Tabata, Yoji |e verfasserin |4 aut | |
700 | 1 | |a Elci, Bilge |e verfasserin |4 aut | |
700 | 1 | |a Brandenberg, Nathalie |e verfasserin |4 aut | |
700 | 1 | |a Kolotuev, Irina |e verfasserin |4 aut | |
700 | 1 | |a Gjorevski, Nikolce |e verfasserin |4 aut | |
700 | 1 | |a Clevers, Hans |e verfasserin |4 aut | |
700 | 1 | |a Lutolf, Matthias P |e verfasserin |4 aut | |
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