Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix
Open accessAbstract
Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease.
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Bioengineered livers produced with dECM scaffolds and liver-composing cells have been extensively developed to replace or regenerate injured liver tissues.
“bioengineered livers produced with dECM scaffolds and liver-composing cells have been extensively developed to replace or regenerate injured liver tissues8,9.”
From Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation (2023) · cites this paper as [8]
The Results and Discussion describe a decellularized liver matrix seeded with hepatocytes, with preliminary endothelial-cell seeding, for a transplantable graft. But the paper calls this a first step toward auxiliary liver grafts; it does not establish that such livers had been extensively developed or had replaced or regenerated injured liver tissue. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe enrichment of laminin in decellularized liver matrices has been explored with the aim of creating transplantable grafts.
“The enrichment of laminin in decellularized liver matrices has been explored with the aim of creating transplantable grafts.[ 126 ]”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [126]
The Results section (Characterization of decellularized liver matrix; page unavailable) reports that laminin-β1 was retained in the decellularized matrix similarly to native liver, not that the matrix was enriched with laminin. The paper also reports developing and transplanting recellularized liver grafts in rats, so the graft objective is supported, but the claimed laminin enrichment is not. (LLM, conf=0.89)
Experimental — accuracy not yet measuredUygun's work yielded transplantable grafts from decellularized liver matrices that supported liver functions including albumin secretion, urea synthesis, and cytochrome P450 activity, and enhanced hepatocyte survival and function post-transplant.
“Uygun's groundbreaking work in 2010 yielded transplantable grafts from decellularized liver matrices that supported liver functions, including albumin secretion, urea synthesis, and cytochrome P450 activity, and enhanced hepatocyte survival and function post‐transplant.[ 126 ]”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [126]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredPerfusion represents an ideal approach for decellularizing large, thick, compact organs like the liver.
“Perfusion, which involves the infusion of chemical or biological agents through the cannulated intrinsic vascular system, represents an ideal approach for decellularizing large, thick, compact organs like the liver [7,12].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
The Results (Characterization of decellularized liver matrix; page unavailable) report successful whole-rat-liver decellularization by portal perfusion with SDS. The Discussion says this preserved liver architecture and vasculature. The paper does not establish that perfusion is the ideal approach for large, thick, compact organs generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPrimary murine hepatocytes have demonstrated the ability to attach, grow, proliferate, and survive within decellularized rodent livers while retaining their morphology and function.
“Primary murine hepatocytes are frequently used for recellularization experiments and have demonstrated the ability to attach, grow, proliferate, and survive within decellularized rodent livers while retaining their morphology and function [12,110,203].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
The Results (Recellularization of decellularized liver matrix; no page available) report that primary rat hepatocytes engrafted in decellularized rat livers and remained viable and functional. The Results (Transplantation of recellularized liver grafts; no page available) report retained normal morphology and hepatic function. The paper does not demonstrate that the hepatocytes grew or proliferated within the matrix. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Uygun et al. found that histological analysis demonstrated the capability of endothelial cells to cover the blood vasculature after seeding the rat liver scaffold with microvascular endothelial cells into the portal vein 24 h after repopulation by hepatocytes and media perfusion for 5 days.
“For example, Uygun et al. attempted to seed the rat liver scaffold with microvascular endothelial cells into the portal vein 24 h after repopulation by hepatocytes and allowed media perfusion for 5 days [12]. Histological analysis demonstrated the capability of the endothelial cells to cover the blood vasculature.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe biliary network tree is confirmed to be intact after decellularization by scan electron microscopy, corrosion cast, dye perfusion, and contrast radiography; only reconstruction by bile duct cells is necessary.
“Fortunately, the biliary network tree is confirmed to be intact after decellularization by scan electron microscopy, corrosion cast, dye perfusion, and contrast radiography; only reconstruction by bile duct cells is necessary [12,110,170,198].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
The Results (Characterization of decellularized liver matrix; page unavailable) use dye perfusion, corrosion casting and scanning electron microscopy to assess the vascular tree, not to confirm an intact biliary tree; they do not report contrast radiography. The Discussion (page unavailable) identifies biliary tract reconstruction as future work, but says an engineered liver will also require other nonparenchymal cells, so it does not support the claim that bile duct cells are all that is necessary. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAfter recellularization with rat hepatocytes, Uygun et al. transplanted the recellularized liver heterotopically for 8 h, and examination revealed the hepatocytes' ability to retain normal morphology and function.
“After recellularization with rat hepatocytes, they transplanted the recellularized liver heterotopically for 8 h. Examination of the graft revealed the hepatocytes’ ability to retain their normal morphology and function.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
In 2010, Uygun et al. demonstrated the feasibility of obtaining a whole decellularized scaffold through perfusion of the rat liver with detergent for 72 h.
“In 2010, Uygun et al. demonstrated the feasibility of obtaining a whole decellularized scaffold through the perfusion of the rat liver with detergent for 72 h [12].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
In a rat model, decellularized liver reseeded with primary rat hepatocytes and anastomosed to recipient renal artery and renal vein for 8 h retained function, normal morphology, and location within the parenchyma of the scaffold.
“The reseeded cells within the scaffold were able to retain function, normal morphology, and location within the parenchyma of the scaffold.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
Over the past 14 years, since Uygun et al. pioneered liver decellularization and recellularization, significant progress has been made in perfusion decellularization/recellularization technology.
“Over the past 14 years, since Uygun et al. pioneered liver decellularization and recellularization, significant progress has been made in perfusion decellularization/recellularization technology [12].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
Peracetic acid (PAA) at 0.1% is the most commonly used acid for decellularization and sterilization of liver, but it has adverse effects on GAGs, growth factors, and mechanical characteristics of ECM.
“Peracetic acid (PAA) at a concentration of 0.1 % is the most commonly used acid for decellularization and sterilization of liver; however, it has adverse effects on GAGs, growth factors, and the mechanical characteristics of ECM [12,15,[103], [104], [105], [106], [107]].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [12]
The Results (Characterization of decellularized liver matrix; page unavailable) describe decellularization by SDS perfusion, not peracetic acid. The Discussion reports a loss of about half the liver’s glycosaminoglycans during that process, but our copy does not address whether 0.1% PAA is commonly used or its effects on GAGs, growth factors, or ECM mechanical characteristics (searched: peracetic acid, PAA, 0.1%, sterilization, growth factors, mechanical properties). (LLM, conf=0.76)
Experimental — accuracy not yet measured
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- Authors
- Uygun, B. E., Soto-Gutierrez, A., Yagi, H., Izamis, M.-L., Guzzardi, M. A., Shulman, C., Milwid, J., Kobayashi, N., Tilles, A., Berthiaume, F., Hertl, M., Nahmias, Y., Yarmush, M. L., & Uygun, K.
- Affiliations
- Harvard University (US)
- Okayama University (JP)
- Massachusetts General Hospital (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Uygun, Korkut
- ORCID
- Venue
- Nature Medicine
- Published
- 2010-06-13
- Volume
- 16
- Issue
- 7
- Pages
- 814-820
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC2930603
- OpenAlex
- W2111338636
- Cited by
- 1,370
- References
- 39
- Citations by year
- 2026: 30 · 2025: 31 · 2024: 59 · 2023: 78 · 2022: 58 · 2021: 92 · 2020: 78 · 2019: 90 · 2018: 96 · 2017: 110 · 2016: 117 · 2015: 127 · 2014: 116 · 2013: 99 · 2012: 95
- FWCI
- 96.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K99DK083556, K99DK080942, K99DK088962, R01 DK59766, R00DK080942, R01DK084053, K99/R00 DK080942, R00DK083556, R01DK059766, R00DK088962)
- 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
- recellularization, hepatocytes, organ shortage, liver failure, hepatocyte viability, albumin secretion, urea synthesis, cytochrome P450
- MeSH terms
- Animals, Extracellular Matrix, Humans, Liver, Liver Circulation, Organ Preservation, Perfusion, Portal Vein, Liver Transplantation, Hepatocytes, Tissue Engineering, Rats
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