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Liver donor age affects hepatocyte function through age-dependent changes in decellularized liver matrix
Open accessAbstract
The only treatment available for end stage liver diseases is orthotopic liver transplantation. Although there is a big donor scarcity, many donor livers are discarded as they do not qualify for transplantation. Alternatively, decellularization of discarded livers can potentially render them transplantable upon recellularization and functional testing. The success of this approach will heavily depend on the quality of decellularized scaffolds which might show variability due to factors including age. Here we assessed the age-dependent differences in liver extracellular matrix (ECM) using rat and human livers. We show that the liver matrix has higher collagen and glycosaminoglycan content and a lower growth factor content with age. Importantly, these changes lead to deterioration in primary hepatocyte function potentially due to ECM stiffening and integrin-dependent signal transduction. Overall, we show that ECM changes with age and these changes significantly affect cell function thus donor age should be considered as an important factor for bioengineering liver substitutes.
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The content of laminin, elastin, and growth factors decreases with age.
“Moreover, the content of laminin, elastin, and growth factors decreases with age [30,37,84,85].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [30]
The Results report that several growth factors were significantly lower in old rat liver matrix, supporting that part of the sentence. But the same section identifies laminins and elastin in old matrix, and the Discussion says laminins were more abundant in old human liver matrix and elastin was detected only in old rat matrix—the opposite of the claimed decrease. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredOne significant disadvantage of using human organs is the age-related changes of the extracellular matrix (ECM).
“One significant disadvantage of using human organs is the age-related changes of the extracellular matrix (ECM) [[30], [31], [32]].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [30]
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Lellouch, A. G. (2022) · theses.fr (ABES) · doi:10.70675/85775456z32d7z4c36z95a3z145139e6e7e1
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A review on decellularization scaffolding for liver regeneration in transplantation
Liu, Y., Liu, S.-Y., Chung, W.-Y., Bowrey, D. J., & Huang, K.-W. (2026) · Hepatoma Research · doi:10.20517/2394-5079.2026.09
Ellis, B. W., Chen, H., Mojoudi, M., Longchamp, A., Yeh, H., Yarmush, M. L., Toner, M., Uygun, K., & Uygun, B. E. (2026) · Cells · doi:10.3390/cells15151334
Self-citationZhang, T., Xu, H., Hao, H., & An, M. (2026) · Applied Materials Today · doi:10.1016/j.apmt.2026.103444
Tissue coordination in ageing and disease
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Metadata
- Authors
- Acun, A., Oganesyan, R., Uygun, K., Yeh, H., Yarmush, M. L., & Uygun, B. E.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Uygun, Basak E.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 270
- Pages
- 120689
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC7906943
- OpenAlex
- W3122728245
- Cited by
- 39
- References
- 57
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 12 · 2023: 7 · 2022: 9 · 2021: 2
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Shriners Hospitals for Children
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- donor age, hepatocyte function, collagen, glycosaminoglycans, growth factors, extracellular matrix stiffness, integrin signaling, orthotopic liver transplantation
- MeSH terms
- Animals, Extracellular Matrix, Liver, Hepatocytes, Tissue Engineering, Rats, Tissue Scaffolds
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