Journal
NATURE
Volume 585, Issue 7826, Pages 574-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-2724-8
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Funding
- Swiss National Science Foundation (SNSF) [310030_179447]
- National Center of Competence in Research (NCCR) 'Bio-Inspired Materials'
- EU
- Personalized Health and Related Technologies (PHRT) Initiative from the ETH Board
- EPFL
- Novartis Foundation for Medical-Biological Research
- EMBO
- Swiss National Science Foundation (SNF) [310030_179447] Funding Source: Swiss National Science Foundation (SNF)
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Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology(1-4). However, the approaches that are used at present to derive these organoids in three-dimensional matrices(5,6)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.
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