The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
3D in vitro morphogenesis of human intestinal epithelium in a gut-on-a-chip or a hybrid chip with a cell culture insert
Open accessAbstract
Human intestinal morphogenesis establishes 3D epithelial microarchitecture and spatially organized crypt-villus characteristics. This unique structure is necessary to maintain intestinal homeostasis by protecting the stem cell niche in the basal crypt from exogenous microbial antigens and their metabolites. Also, intestinal villi and secretory mucus present functionally differentiated epithelial cells with a protective barrier at the intestinal mucosal surface. Thus, re-creating the 3D epithelial structure is critical to building in vitro intestine models. Notably, an organomimetic gut-on-a-chip can induce spontaneous 3D morphogenesis of an intestinal epithelium with enhanced physiological function and biomechanics. Here we provide a reproducible protocol to robustly induce intestinal morphogenesis in a microfluidic gut-on-a-chip as well as in a Transwell-embedded hybrid chip. We describe detailed methods for device fabrication, culture of Caco-2 or intestinal organoid epithelial cells in conventional setups as well as on microfluidic platforms, induction of 3D morphogenesis and characterization of established 3D epithelium using multiple imaging modalities. This protocol enables the regeneration of functional intestinal microarchitecture by controlling basolateral fluid flow within 5 d. Our in vitro morphogenesis method employs physiologically relevant shear stress and mechanical motions, and does not require complex cellular engineering or manipulation, which may be advantageous over other existing techniques. We envision that our proposed protocol may have a broad impact on biomedical research communities, providing a method to regenerate in vitro 3D intestinal epithelial layers for biomedical, clinical and pharmaceutical applications.
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Self-citationReplication of human noroviruses in stem cell–derived human enteroids
Ettayebi, K., Crawford, S. E., Murakami, K., Broughman, J. R., Karandikar, U., Tenge, V. R., Neill, F. H., Blutt, S. E., Zeng, X.-L., Qu, L., et al. (2016) · Science · doi:10.1126/science.aaf5211 · Cited by 1,305
Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications
Sato, T., & Clevers, H. (2013) · Science · doi:10.1126/science.1234852 · Cited by 1,170
Kim, H. J., Li, H., Collins, J. J., & Ingber, D. E. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522193112 · Cited by 922
Self-citationHomeostatic mini-intestines through scaffold-guided organoid morphogenesis
Nikolaev, M., Mitrofanova, O., Broguiere, N., Geraldo, S., Dutta, D., Tabata, Y., Elci, B., Brandenberg, N., Kolotuev, I., Gjorevski, N., et al. (2020) · Nature · doi:10.1038/s41586-020-2724-8 · Cited by 755
Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids
Kasendra, M., Tovaglieri, A., Sontheimer-Phelps, A., Jalili-Firoozinezhad, S., Bein, A., Chalkiadaki, A., Scholl, W., Zhang, C., Rickner, H., Richmond, C. A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-21201-7 · Cited by 754
Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation
Kim, H. J., & Ingber, D. E. (2013) · Integrative Biology · doi:10.1039/c3ib40126j · Cited by 750
Microfabrication of human organs-on-chips
Huh, D., Kim, H. J., Fraser, J. P., Shea, D. E., Khan, M., Bahinski, A., Hamilton, G. A., & Ingber, D. E. (2013) · Nature Protocols · doi:10.1038/nprot.2013.137 · Cited by 712
Self-citationMicrofluidic Organ-on-a-Chip Models of Human Intestine
Bein, A., Shin, W., Jalili-Firoozinezhad, S., Park, M. H., Sontheimer-Phelps, A., Tovaglieri, A., Chalkiadaki, A., Kim, H. J., & Ingber, D. E. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.12.010 · Cited by 625
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Cited by
Organoids: The current status and biomedical applications
Yang, S., Hu, H., Kung, H., Zou, R., Dai, Y., Hu, Y., Wang, T., Lv, T., Yu, J., & Li, F. (2023) · MedComm · doi:10.1002/mco2.274 · Cited by 266
Organoids in gastrointestinal diseases: From experimental models to clinical translation
Günther, C., Winner, B., Neurath, M. F., & Stappenbeck, T. S. (2022) · Gut · doi:10.1136/gutjnl-2021-326560 · Cited by 145
Microfluidic high-throughput 3D cell culture
Ko, J., Park, D., Lee, J., Jung, S., Baek, K., Sung, K. E., Lee, J., & Jeon, N. L. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00163-8 · Cited by 88
Kimura, H., Nakamura, H., Goto, T., Uchida, W., Uozumi, T., Nishizawa, D., Shinha, K., Sakagami, J., & Doi, K. (2024) · Lab on a Chip · doi:10.1039/d3lc00934c · Cited by 20
Metadata
- Authors
- Shin, W., & Kim, H. J.
- Venue
- Nature Protocols
- Published
- 2022-02-02
- Volume
- 17
- Issue
- 3
- Pages
- 910-939
- ISSN
- 1750-2799 (ISSN-L)
- 1754-2189
- OpenAlex
- W4210775727
- Cited by
- 185
- References
- 14
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Shin, W., & Kim, H. J. (2022). 3D in vitro morphogenesis of human intestinal epithelium in a gut-on-a-chip or a hybrid chip with a cell culture insert. Nature Protocols. https://doi.org/10.1038/s41596-021-00674-3
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