Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture
Open accessAbstract
Organoids have extensive therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, their clinical application is greatly limited by the lack of effective GMP-compliant systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix (ECM) hydrogels derived from decellularized tissues (DT) can provide an environment capable of directing cell growth. These gels possess the biochemical signature of tissue-specific ECM and have the potential for clinical translation. Gels from decellularized porcine small intestine (SI) mucosa/submucosa enable formation and growth of endoderm-derived human organoids, such as gastric, hepatic, pancreatic, and SI. ECM gels can be used as a tool for direct human organoid derivation, for cell growth with a stable transcriptomic signature, and for in vivo organoid delivery. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically.
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Giobbe et al. showed that gels from decellularized porcine small intestine mucosa/submucosa could support the formation and growth of endoderm-derived human organoids, including gastric, liver, pancreatic, and SI organoids.
“For example, Giobbe et al. showed that gels from decellularized porcine small intestine mucosa/submucosa could support the formation and growth of endoderm‐derived human organoids, including gastric, liver, pancreatic, and SI organoids.”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [195]
ECM hydrogels act as tools for direct human organoid derivation, cell growth with stable transcriptomic features, and for facilitating in vivo organoid delivery.
“ECM hydrogels act as tools for direct human organoid derivation, cell growth with stable transcriptomic features, and for facilitating in vivo organoid delivery.[ 195 ]”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [195]
Several alternative methods have highlighted advantages of replacing Matrigel with tissue-relevant ECM components for other organs.
“Several alternative methods have highlighted advantages of replacing Matrigel with tissue-relevant ECM components for other organs [16,21,22].”
A porcine intestinal ECM gel supported the formation of enteroids from murine Lgr5+ crypt cells and from human pediatric stomach and intestinal crypts.
“The porcine intestinal ECM gel was able to support the formation of enteroids from murine Lgr5+ crypt cells, and from human pediatric stomach and intestinal crypts.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [80]
The porcine intestinal ECM gel is applicable to grow organoids from the liver, stomach, and pancreas.
“This intestinal ECM gel is also applicable to grow organoids from the liver, stomach, and pancreas80.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [80]
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- Authors
- Giobbe, G. G., Crowley, C., Luni, C., Campinoti, S., Khedr, M., Kretzschmar, K., De Santis, M. M., Zambaiti, E., Michielin, F., Meran, L., Hu, Q., van Son, G., Urbani, L., Manfredi, A., Giomo, M., Eaton, S., Cacchiarelli, D., Li, V. S. W., Clevers, H., Bonfanti, P., Elvassore, N., & De Coppi, P.
- Affiliations
- University College London (GB)
- ShanghaiTech University (CN)
- The Francis Crick Institute (GB)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Telethon Institute Of Genetics And Medicine (IT)
- University of Padua (IT)
- Corresponding author
- Elvassore, Nicola
- ORCID
- Giobbe, Giovanni Giuseppe
- Crowley, Claire
- Luni, Camilla
- Campinoti, Sara
- Khedr, Moustafa
- Kretzschmar, Kai
- De Santis, Martina Maria
- Zambaiti, Elisa
- Michielin, Federica
- Meran, Laween
- Hu, Qianjiang
- Urbani, Luca
- Manfredi, Anna
- Giomo, Monica
- Eaton, Simon
- Cacchiarelli, Davide
- Li, Vivian S. W.
- Clevers, Hans
- Bonfanti, Paola
- Elvassore, Nicola
- De Coppi, Paolo
- Venue
- Nature Communications
- Published
- 2019-12-11
- Volume
- 10
- Issue
- 1
- Pages
- 5658-5658
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6906306
- OpenAlex
- W2996112306
- Cited by
- 500
- References
- 56
- Citations by year
- 2026: 52 · 2025: 84 · 2024: 93 · 2023: 69 · 2022: 75 · 2021: 84 · 2020: 42 · 2019: 1
- FWCI
- 48.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
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- RePEc: Research Papers in Economics (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- The Francis Crick Institute (cc-by)
- Funders
- Oak Foundation (W1095/OCAY-14-191)
- DH | National Institute for Health Research (Catalyst Fellowship - Project 2307873 - 17DS11, Professorship)
- Great Ormond Street Hospital Charity (V6116)
- Human Frontier Science Program (HFSPO, LT771/2015)
- Rosetrees Trust (M362-F1)
- Università degli Studi di Padova (PRAT)
- EC | Horizon 2020 Framework Programme (INTENS 668294)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- extracellular matrix hydrogel, decellularized tissue, organoid culture, gastric organoids, hepatic organoids, pancreatic organoids, regenerative medicine, clinical translation
- MeSH terms
- Animals, Endoderm, Extracellular Matrix, Humans, Organoids, Swine, Hydrogels, Tissue Engineering, Cell Proliferation, Tissue Scaffolds
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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