Functional characterization of a bioengineered liver after heterotopic implantation in pigs
Open accessAbstract
Organ bioengineering offers a promising solution to the persistent shortage of donor organs. However, the progression of this technology toward clinical use has been hindered by the challenges of reconstituting a functional vascular network, directing the engraftment of specific functional cell types, and defining appropriate culture conditions to concurrently support the health and phenotypic stability of diverse cell lineages. We previously demonstrated the ability to functionally reendothelialize the vasculature of a clinically scaled decellularized liver scaffold with human umbilical vein endothelial cells (HUVECs) and to sustain continuous perfusion in a large animal recovery model. We now report a method for seeding and engrafting primary porcine hepatocytes into a bioengineered liver (BEL) scaffold previously reendothelialized with HUVECs. The resulting BELs were competent for albumin production, ammonia detoxification and urea synthesis, indicating the presence of a functional hepatocyte compartment. BELs additionally slowed ammonia accumulation during in vivo perfusion in a porcine model of surgically induced acute liver failure. Following explant of the graft, BEL parenchyma showed maintenance of canonical endothelial and hepatocyte markers. Taken together, these results support the feasibility of engineering a clinically scaled functional BEL and establish a platform for optimizing the seeding and engraftment of additional liver specific cells.
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In pigs, a decellularized liver scaffold previously reendothelialized with HUVECs and reseeded with primary porcine hepatocytes, implanted in auxiliary position caudal to the native liver, had functional hepatocytes that produced albumin, detoxified ammonia, and synthesized urea for up to 48 h.
“Repopulated hepatocytes within the bioengineered liver were functional and able to produce albumin, detoxify ammonia, and synthesize urea for up to 48 h.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [193]
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Experimental — accuracy not yet measuredAnderson et al. demonstrated that primary hepatocytes cultured alone or co-cultured with HUVECs exhibited substantial ammonia clearance and urea release in decellularized porcine liver scaffolds.
“Anderson et al. demonstrated that both primary hepatocytes, when cultured alone or co-cultured with human umbilical vein endothelial cells (HUVECs), exhibited substantial ammonia clearance and urea release, indicating the ability of hepatocytes to retain their function in high-density cultures within decellularized porcine liver scaffolds [193].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [193]
The use of primary hepatocytes has shown reproducibility but has only yielded initial signs of significant function, such as temporary stabilization of serum ammonia in one of our in vivo studies.
“The use of primary hepatocytes has shown reproducibility but has only yielded initial signs of significant function, such as temporary stabilization of serum ammonia in one of our in vivo studies [193].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [193]
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- Authors
- Anderson, B. D., Nelson, E. D., Joo, D., Amiot, B. P., Katane, A. A., Mendenhall, A., Steiner, B. G., Stumbras, A. R., Nelson, V. L., Palumbo, R. N., Gilbert, T. W., Davidow, D. S., Ross, J. J., & Nyberg, S. L.
- Affiliations
- Miromatrix Medical (United States) (US)
- Mayo Clinic (US)
- Corresponding author
- Nyberg, Scott L.
- ORCID
- Venue
- Communications Biology
- Published
- 2021-10-07
- Volume
- 4
- Issue
- 1
- Pages
- 1157-1157
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC8497596
- OpenAlex
- W3203717619
- Cited by
- 29
- References
- 20
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 1
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-12-08)
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106667)
- 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
- decellularized liver scaffold, re-endothelialization, human umbilical vein endothelial cells, albumin synthesis, ammonia detoxification, urea synthesis, acute liver failure, large animal model
- MeSH terms
- Animals, Disease Models, Animal, Humans, Liver, Perfusion, Liver Transplantation, Liver Failure, Acute, Hepatocytes, Tissue Engineering, Sus scrofa, Human Umbilical Vein Endothelial Cells
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