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

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:585

Enthalten in:

Nature - 585(2020), 7826 vom: 16. Sept., Seite 574-578

Sprache:

Englisch

Beteiligte Personen:

Nikolaev, Mikhail [VerfasserIn]
Mitrofanova, Olga [VerfasserIn]
Broguiere, Nicolas [VerfasserIn]
Geraldo, Sara [VerfasserIn]
Dutta, Devanjali [VerfasserIn]
Tabata, Yoji [VerfasserIn]
Elci, Bilge [VerfasserIn]
Brandenberg, Nathalie [VerfasserIn]
Kolotuev, Irina [VerfasserIn]
Gjorevski, Nikolce [VerfasserIn]
Clevers, Hans [VerfasserIn]
Lutolf, Matthias P [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Research Support, Non-U.S. Gov't

Anmerkungen:

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

doi:

10.1038/s41586-020-2724-8

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM31510645X