Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues
Open accessAbstract
Organoid technology has provided unique insights into human organ development, function, and diseases. Patient-derived organoids are increasingly used for drug screening, modeling rare disorders, designing regenerative therapies, and understanding disease pathogenesis. However, the use of Matrigel to grow organoids represents a major challenge in the clinical translation of organoid technology. Matrigel is a poorly defined mixture of extracellular matrix proteins and growth factors extracted from the Engelbreth-Holm-Swarm mouse tumor. The extracellular matrix is a major driver of multiple cellular processes and differs significantly between tissues as well as in healthy and disease states of the same tissue. Therefore, we envisioned that the extracellular matrix derived from a native healthy tissue would be able to support organoid growth akin to organogenesis in vivo. Here, we have developed hydrogels from decellularized human and bovine endometrium. These hydrogels supported the growth of mouse and human endometrial organoids, which was comparable to Matrigel. Organoids grown in endometrial hydrogels were proteomically more similar to the native tissue than those cultured in Matrigel. Proteomic and Raman microspectroscopy analyses showed that the method of decellularization affects the biochemical composition of hydrogels and, subsequently, their ability to support organoid growth. The amount of laminin in hydrogels correlated with the number and shape of organoids. We also demonstrated the utility of endometrial hydrogels in developing solid scaffolds for supporting high-throughput, cell culture-based applications. In summary, endometrial hydrogels overcome a major limitation of organoid technology and greatly expand the applicability of organoids to understand endometrial biology and associated pathologies.
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Jamaluddin et al. were the first to use confocal Raman imaging to detect collagen, glycosaminoglycans (GAGs), and amino acids in decellularized scaffolds from bovine and human endometrium.
“Jamaluddin et al. were the first to use confocal Raman imaging to detect components such as collagen, glycosaminoglycans (GAGs), and amino acids in decellularized scaffolds from bovine and human endometrium.[ 107 ]”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [107]
The Results section, “Biochemical Characterization of Endometrium-Derived ECM” (Fig. 2; page not provided), reports confocal Raman analysis of decellularized bovine endometrium and identifies peaks for phenylalanine, GAGs, and collagen. It does not establish that the authors were the first to use this method or report the Raman finding for human endometrium. (LLM, conf=0.87)
Experimental — accuracy not yet measuredJamaluddin et al. fabricated three hydrogels from endometrial ECM and evaluated their quality based on organoid formation efficiency, shape, and size.
“Jamaluddin et al. fabricated three hydrogels from endometrial ECM and evaluated their quality based on organoid formation efficiency, shape, and size.[ 107 ]”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [107]
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Decellularization of tissues and organs
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Liu, J., Song, Q., Yin, W., Li, C., An, N., Le, Y., Wang, Q., Feng, Y., Hu, Y., & Wang, Y. (2025) · Exploration · doi:10.1002/exp.20230078 · Cited by 140 · see citing works
- Authors
- Jamaluddin, M. F. B., Ghosh, A., Ingle, A., Mohammed, R., Ali, A., Bahrami, M., Kaiko, G., Gibb, Z., Filipe, E. C., Cox, T. R., Boulton, A., O’Sullivan, R., Ius, Y., Karakoti, A., Vinu, A., Nahar, P., Jaaback, K., Bansal, V., & Tanwar, P. S.
- Affiliations
- Hunter Medical Research Institute (AU)
- RMIT University (AU)
- Garvan Institute of Medical Research (AU)
- John Hunter Hospital (AU)
- University of Newcastle Australia (AU)
- Corresponding author
- Tanwar, Pradeep S.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2022-10-24
- Volume
- 119
- Issue
- 44
- Pages
- e2208040119-e2208040119
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC9636948
- OpenAlex
- W4307188010
- Cited by
- 84
- References
- 3
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 20 · 2023: 21 · 2022: 1 · 2016: 1
- FWCI
- 14.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- Cancer Australia (1187542)
- Department of Health | National Health and Medical Research Council (1159094)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- endometrial organoids, bovine endometrium, human endometrium, Matrigel alternative, extracellular matrix, laminin, micro-Raman spectroscopy, endometrial cancer, organoid culture
- MeSH terms
- Animals, Cattle, Endometrium, Female, Humans, Laminin, Neoplasms, Organoids, Hydrogels, Proteomics
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