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The use of whole organ decellularization for the generation of a vascularized liver organoid
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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“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].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [13]
In the citing paper
“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.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [13]
In the citing paper
“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].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [13]
In the citing paper
“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.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [13]
In the citing paper
“Baptista et al. demonstrated the capacity of decellularized livers to induce the differentiation of fetal hepatoblasts into biliary and hepatocytic lineages [13].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [13]
In the citing paper
“Cell lines, including HUVECs and EA. hy926 cells, have been extensively used for reendothelization of decellularized livers due to their relative ease of accessibility and the non-invasive harvesting from medical waste, in addition to a high yield following isolation [10,13,14,235].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [13]
In the citing paper
“In contrast, Baptista and colleagues perfused Triton X-100 and ammonium hydroxide through a ferret hepatic vascular network to remove cells. This method preserved the underlying ECM and vasculature while retaining most of the glycosaminoglycans, collagens, and elastins.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [74]
In the citing paper
“The decellularized material could be colonized by human fetal liver and endothelial cells to produce a functioning organoid74.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [74]
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Metadata
- 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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