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Cited by 31Tissue Engineering and Regenerative Medicine3D Printing in Biomedical ResearchOrgan Transplantation Techniques and Outcomes

Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model

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Higashi, Hisanobu, Yagi, Hiroshi, Kuroda, Kohei, Tajima, Kazuki, Kojima, Hideaki, Nishi, Kotaro, Morisaku, Toshinori, Hirukawa, Kazuya +11 more·2022·American Journal of Transplantation
DOI 10.1111/ajt.16928PMC PMC9008767
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Abstract

Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.

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Authors
Higashi, H., Yagi, H., Kuroda, K., Tajima, K., Kojima, H., Nishi, K., Morisaku, T., Hirukawa, K., Fukuda, K., Matsubara, K., Kitago, M., Shinoda, M., Obara, H., Adachi, S., Nishimura, K., Natsume, T., Tomi, M., Soto-Gutierrez, A., & Kitagawa, Y.
Affiliations
  • Keio University (JP)
  • National Institute of Advanced Industrial Science and Technology (JP)
Corresponding author
Yagi, Hiroshi
ORCID
Venue
American Journal of Transplantation
Publisher
Elsevier BV
Published
2022-03
Volume
22
Issue
3
Pages
731-744
ISSN
1600-6135 (ISSN-L)
DOI
10.1111/ajt.16928
PMC
PMC9008767
OpenAlex
W4200175842
Cited by
31
References
6
Citations by year
2026: 7 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 5
FWCI
4.46
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Transplantation (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Japan Agency for Medical Research and Development (17bm0404004h0005, 18bm0404038h0001)
  • NIH Clinical Center (DK096990, DK099257, DK117881, DK119973, TR002383, TR003289)
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
liver transplantation, hepatocyte repopulation, endothelial cell seeding, liver-specific gene expression, large animal model
MeSH terms
Animals, Liver, Swine, Liver Transplantation, Liver Failure, Hepatocytes, Tissue Engineering, Endothelial Cells, Tissue Scaffolds

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