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Cited by 19Tissue Engineering and Regenerative Medicine3D Printing in Biomedical ResearchLiver physiology and pathology

Repopulation of intrahepatic bile ducts in engineered rat liver grafts

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Chen, Yibin, Devalliere, Julie, Bulutoglu, Beyza, Yarmush, Martin L., Uygun, Basak E.·2019·TECHNOLOGY
DOI 10.1142/s2339547819500043PMC PMC6684151
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Abstract

Engineered liver grafts for transplantation with sufficient hepatic function have been developed both in small and large animal models using the whole liver engineering approach. However, repopulation of the bile ducts in the whole liver scaffolds has not been addressed yet. In this study, we show the feasibility of repopulating the bile ducts in decellularized rat livers. Biliary epithelial cells were introduced into the bile ducts of the decellularized liver scaffolds with or without hepatocytes in the parenchymal space. The recellularized grafts were cultured under perfusion for up to 2 days and histological analysis revealed that the biliary epithelial cells formed duct-like structures, with the viable hepatocyte mass residing in the parenchymal space, in an arrangement highly comparable to the native tissue. The grafts were viable and functional as confirmed by both albumin and urea assay results and the gene expression analysis of biliary epithelial cells in recellularized liver grafts. This study provides the proof-of-concept results for rat liver grafts co-populated with parenchymal and biliary epithelial cells.

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  • The biliary tree within the decellularized liver scaffold remains almost impermeable and closed at the ends of the smallest ductules, allowing retention of any liquid injected into the extrahepatic bile duct without diffusion into the parenchyma.

    “Importantly, they reported that the biliary tree within the decellularized liver scaffold remains almost impermeable and closed at the ends of the smallest ductules, allowing the retention of any liquid injected into the extrahepatic bile duct without diffusion into the parenchyma.”

    From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [111]

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  • After 48 h of dynamic perfusion, biliary epithelial cells formed duct-like structures, with viable hepatocyte mass residing in the parenchymal space, in an arrangement mimicking native tissue.

    “After 48 h of dynamic perfusion, they observed that the biliary epithelial cells formed duct-like structures, with the viable hepatocyte mass residing in the parenchymal space, in an arrangement mimicking the native tissue.”

    From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [111]

  • Compared to decellularized livers reseeded by hepatocytes only, scaffolds recellularized with both cholangiocytes and hepatocytes revealed slightly higher levels of cumulative albumin production and urea secretion.

    “Interestingly, compared to decellularized livers reseeded by hepatocytes only, scaffolds recellularized with both cholangiocytes and hepatocytes revealed slightly higher levels of cumulative albumin production and urea secretion.”

    From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [111]

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Cited by

Sorted by citations

Authors
Chen, Y., Devalliere, J., Bulutoglu, B., Yarmush, M. L., & Uygun, B. E.
Affiliations
  • Harvard University (US)
  • Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, Boston, MA 02114, USA
  • Rutgers, The State University of New Jersey (US)
ORCID
Venue
TECHNOLOGY
Publisher
World Scientific Pub Co Pte Ltd
Published
2019-03
Volume
07
Issue
01n02
Pages
46-55
ISSN
  • 2339-5478 (ISSN-L)
  • 2345-7740
DOI
10.1142/s2339547819500043
PMC
PMC6684151
OpenAlex
W2963721969
Cited by
19
References
0
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 2
FWCI
2.63
Type
journal article
Language
en
Open access
Locations
  • TECHNOLOGY (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (K99DK088962, R01DK084053, 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
decellularized liver scaffold, cholangiocytes, hepatocytes, recellularization, perfusion culture, liver transplantation, rat liver, biliary differentiation

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