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Nonadhesive Alginate Hydrogels Support Growth of Pluripotent Stem Cell-Derived Intestinal Organoids
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Abstract
Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell instructive properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. In addition, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.
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“Mechanical properties, e.g., ECM stiffness, of the cell and tissue microenvironment are known to play an important role in cell survival [53,54], proliferation[55], migration[56], and tissue differentiation[57,58].”
In the citing paper
“Organoid types grown in alginate include human lung99,100, human brain101, murine intestinal102, human intestinal102,103, human pancreatic104, and human and murine vascular105.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [103]
In the citing paper
“In addition to organoids grown in naturally-derived proteins, several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [103]
In the citing paper
“Capeling and colleagues grew HIOs on an alginate substrate and found that differentiation of human pluripotent cells into HIOs could be supported without the alginate providing chemical cues to the cells.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [103]
In the citing paper
“There have been a number of studies showing that organoids can be grown on unmodified surfaces such as alginate, but this requires more research103,105,110,175,183.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [103]
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Metadata
- Authors
- Capeling, M. M., Czerwinski, M., Huang, S., Tsai, Y.-H., Wu, A., Nagy, M. S., Juliar, B., Sundaram, N., Song, Y., Han, W. M., Takayama, S., Alsberg, E., Garcia, A. J., Helmrath, M., Putnam, A. J., & Spence, J. R.
- Affiliations
- University of Michigan (US)
- Cincinnati Children's Hospital Medical Center (US)
- Georgia Institute of Technology (US)
- Case Western Reserve University (US)
- Corresponding author
- Spence, Jason R.
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 12
- Issue
- 2
- Pages
- 381-394
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC6373433
- OpenAlex
- W2949559557
- Cited by
- 226
- References
- 50
- Citations by year
- 2026: 11 · 2025: 39 · 2024: 19 · 2023: 30 · 2022: 35 · 2021: 45 · 2020: 33 · 2019: 14
- FWCI
- 10.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Intestinal Stem Cell Consortium (U01DK103141)
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- Novel Alternative Model Systems for Enteric Diseases (U19AI116482)
- Cellular and Biotechnology Training Program (T32GM008353)
- Training Program in Organogenesis Fellowship (T32HD007505)
- NICHD (R24HD000836)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- human intestinal organoids, alginate hydrogel, extracellular matrix mimics, pluripotent stem cells, organoid transplantation, mechanical support, organoid maturation
- MeSH terms
- Alginates, Animals, Cell Differentiation, Cell Line, Collagen, Drug Combinations, Epithelium, Extracellular Matrix, Humans, Intestines, Laminin, Organoids, Proteoglycans, Mice, SCID, Mice, Inbred NOD, Hydrogels, Tissue Engineering, Pluripotent Stem Cells, Mice
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