Cited by 681Tissue Engineering and Regenerative Medicine3D Printing in Biomedical ResearchLiver physiology and pathology

The use of whole organ decellularization for the generation of a vascularized liver organoid

Baptista, Pedro M., Siddiqui, Mohummad M., Lozier, Genevieve, Rodriguez, Sergio R., Atala, Anthony, Soker, Shay·2011·Hepatology

Abstract

UNLABELLED: A major roadblock to successful organ bioengineering is the need for a functional vascular network within the engineered tissue. Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. Livers from different species were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network. The decellularized vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. The vascular network was used to reseed the scaffolds with human fetal liver and endothelial cells. These cells engrafted in their putative native locations within the decellularized organ and displayed typical endothelial, hepatic, and biliary epithelial markers, thus creating a liver-like tissue in vitro. CONCLUSION: These results represent a significant advancement in the bioengineering of whole organs. This technology may provide the necessary tools to produce the first fully functional bioengineered livers for organ transplantation and drug discovery.

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Registry

Crossref · 10.1002/hep.24067

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42 of 42 references verified0 citation errors · 0 not checkable

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  • Perfusion retains the inherent vascular network (portal vein, hepatic artery, and hepatic veins), necessary for the transportation of nutrients and oxygen within liver during recellularization and post-transplantation in vivo.

    “Moreover, perfusion retains the inherent vascular network (portal vein, hepatic artery, and hepatic veins), necessary for the transportation of nutrients and oxygen within liver during the recellularization process and post-transplantation in vivo [13,14,168].”
  • When cells are reseeded through the portal vein, they are observed in the periportal area; when seeded through the vena cava, they are deposited in the pericentral area.

    “Upon reseeding the cells through the portal vein, the cells were observed in the periportal area, whereas when seeded through the vena cava, they were deposited in the pericentral area.”
  • Baptista et al. reseeded the ferret liver scaffold with fluorescently labeled ECs through antegrade infusion via the portal vein or retrograde cell infusion through vena cava to investigate the distribution and localization of endothelial cells within the parenchymal and nonparenchymal spaces.

    “Additionally, Baptista et al. reseeded the ferret liver scaffold with fluorescently labeled ECs through antegrade infusion via the portal vein or retrograde cell infusion through vena cava to investigate the distribution and localization of endothelial cells within the parenchymal and nonparenchymal spaces [13].”
  • Both HUVECs and EA. hy926 cells were able to line the blood vessels of decellularized livers, with a significant reduction in platelet adhesion and clot formation during ex vivo blood perfusion, and demonstrated the ability to withstand blood flow after in vivo transplantation in pigs.

    “Both cell types were able to line the blood vessels of decellularized livers, with a significant reduction in platelet adhesion and clot formation during ex vivo blood perfusion and demonstrated the ability to withstand blood flow after in vivo transplantation in pigs.”
  • Decellularized livers can induce differentiation of fetal hepatoblasts into biliary and hepatocytic lineages.

    “Baptista et al. demonstrated the capacity of decellularized livers to induce the differentiation of fetal hepatoblasts into biliary and hepatocytic lineages [13].”

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Authors
Baptista, P. M., Siddiqui, M. M., Lozier, G., Rodriguez, S. R., Atala, A., & Soker, S.
Affiliations
  • Wake Forest University Health Sciences (US)
  • Howard Hughes Medical Institute (US)
  • Rice University (US)
  • Mexican Social Security Institute (MX)
Venue
Hepatology
Published
2011-01-10
Volume
53
Issue
2
Pages
604-617
ISSN
0270-9139 (ISSN-L)
OpenAlex
W2065657273
Cited by
681
References
43
Citations by year
2026: 19 · 2025: 16 · 2024: 31 · 2023: 43 · 2022: 27 · 2021: 51 · 2020: 44 · 2019: 52 · 2018: 59 · 2017: 56 · 2016: 62 · 2015: 65 · 2014: 43 · 2013: 56 · 2012: 39
FWCI
38.31
Type
journal article
Language
en
Open access
closed
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Howard Hughes Medical Institute
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
human fetal liver, cholangiocytes, organ transplantation, drug discovery
MeSH terms
Animals, Blood Vessels, Endothelium, Vascular, Ferrets, Humans, Liver, Organoids, Rabbits, Swine, Rats, Sprague-Dawley, Models, Animal, Tissue Engineering, Mice, Rats, Tissue Scaffolds, Bioengineering

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