Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells
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The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg −/− ) rats.
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Human iPSC-derived vascular ECs reseeded into rat decellularized liver engrafted in the scaffold's vascular structure and showed enhanced expression of angiogenesis and anticoagulation-related genes and functions in the organ-like environment.
“The cells engrafted in the scaffold's vascular structure and showed enhanced expression of angiogenesis and anticoagulation-related genes and functions in the organ-like environment.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [242]
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Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver graftsPreprint
Tomofuji, K., Fukumitsu, K., Kondo, J., Horie, H., Makino, K., Wakama, S., Ito, T., Oshima, Y., Ogiso, S., Ishii, T., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.14.468338 · Cited by 1 · see citing works
Self-citation
- Authors
- Takeishi, K., Collin de l’Hortet, A., Wang, Y., Handa, K., Guzman-Lepe, J., Matsubara, K., Morita, K., Jang, S., Haep, N., Florentino, R. M., Yuan, F., Fukumitsu, K., Tobita, K., Sun, W., Franks, J., Delgado, E. R., Shapiro, E. M., Fraunhoffer, N. A., Duncan, A. W., Yagi, H., Mashimo, T., Fox, I. J., & Soto-Gutierrez, A.
- Affiliations
- Kyushu University (JP)
- University of Pittsburgh (US)
- Universidade Federal de Minas Gerais (BR)
- Michigan State University (US)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Keio University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 31
- Issue
- 9
- Pages
- 107711
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7734598
- OpenAlex
- W3032600724
- Cited by
- 118
- References
- 76
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 24 · 2023: 20 · 2022: 31 · 2021: 22 · 2020: 4
- FWCI
- 17.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Conicet (submittedVersion, cc-by-nc-nd)
- Funders
- Université Pierre et Marie Curie (P30CA047904)
- American Liver Foundation (PCT/US2018/018032, WO/2015/168254, WO/2011/002926)
- University of Pittsburgh
- National Institutes of Health (HSN276201200017C, DK117881, DK103645, DK107697, DK119973, TR002383, P30DK120531, DK099257, P30CA047904)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- induced pluripotent stem cells, auxiliary liver transplantation, iPSC-derived hepatocytes, iPSC-derived endothelial cells, rat model
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Fetus, Fibroblasts, Humans, Male, Transcription Factors, Fibroblast Growth Factor 2, Immunocompromised Host, Rats, Sprague-Dawley, Hepatocytes, Tissue Engineering, Activins, Rats, Tissue Scaffolds, Bone Morphogenetic Protein 4, Induced Pluripotent Stem Cells, Cellular Reprogramming
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