Homeostatic mini-intestines through scaffold-guided organoid morphogenesis
Open accessAbstract
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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Microfluidic systems have been used to create miniaturized cellular models comprising organoids that recapitulate critical aspects of organ physiology, termed organ-on-a-chip.
“Microfluidic systems have been used to create miniaturized cellular models comprising organoids that recapitulate critical aspects of organ physiology, termed organ-on-a-chip99 (OoC).”
From Organoids (2022) · cites this paper as [99]
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- Authors
- 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.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- University of Lausanne (CH)
- F. Hoffmann-La Roche AG (CH)
- Royal Netherlands Academy of Arts and Sciences (NL)
- ORCID
- Venue
- Nature
- Published
- 2020-09-16
- Volume
- 585
- Issue
- 7826
- Pages
- 574-578
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3087653149
- Cited by
- 755
- References
- 56
- Citations by year
- 2026: 95 · 2025: 127 · 2024: 141 · 2023: 131 · 2022: 131 · 2021: 117 · 2020: 12
- FWCI
- 30.80
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- intestinal organoids, organoid morphogenesis, intestinal stem cells, self-organization, host-microbe interactions, gut microbiota colonization, tissue regeneration
- MeSH terms
- Human Embryonic Stem Cells, Animals, Cell Differentiation, Homeostasis, Humans, Intestines, Models, Biological, Morphogenesis, Organoids, Regeneration, Stem Cells, Cryptosporidium parvum, Cell Lineage, Body Patterning, Tissue Engineering, Regenerative Medicine, Tissue Culture Techniques, Mice, Tissue Scaffolds, Human Umbilical Vein Endothelial Cells
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