Efficient recellularisation of decellularised whole-liver grafts using biliary tree and foetal hepatocytes
Open accessAbstract
A whole-organ regeneration approach, using a decellularised xenogeneic liver as a scaffold for the construction of a transplantable liver was recently reported. Deriving suitable scaffolds was the first step towards clinical application; however, effective recellularisation remains to be achieved. This report presents a strategy for the improvement of the recellularisation process, using novel cell-seeding technique and cell source. We evaluated recellularised liver grafts repopulated through the portal vein or the biliary duct with mice adult hepatocytes or E14.5 foetal hepatocytes. More than 80% of the cells seeded through the biliary tree entered the parenchyma beyond the ductule-lining matrix barrier and distributed throughout the liver lobule. In contrast, about 20% of the cells seeded through the portal tree entered the parenchyma. The gene expression levels of foetal hepatocyte albumin, glucose 6-phosphatase, transferrin, cytokeratin 19, and gamma-glutamyl transpeptidase were increased in three-dimensional cultures in the native liver-derived scaffolds, and the activation of liver detoxification enzymes and formation of biliary duct-like structures were supported. The metabolic functions of liver grafts recellularised with different cell types were similar. These results suggest that biliary tree cell-seeding approach is promising, and that liver progenitor cells represent a good cell source candidate.
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Perfusion crosslinking via both portal vein and bile duct is beneficial for distributing NGOs evenly throughout dECM scaffolds.
“perfusion crosslinking via both portal vein and bile duct was beneficial for distributing NGOs evenly throughout dECM scaffolds, according to the previous report27.”
From Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation (2023) · cites this paper as [27]
The Results section on seeding routes (page unavailable) compares portal-vein and bile-duct delivery into decellularised liver scaffolds, but finds substantially better parenchymal distribution after bile-duct seeding. The Discussion suggests multiple routes may help arrange cells spatially; neither section evaluates perfusion crosslinking or the even distribution of NGOs. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOrgan-specific cell-ECM communication enhanced maturation of reseeded fetal hepatocytes within decellularized rat livers into both hepatocyte and cholangiocyte lineages, without addition of pro-differentiation signals during 7 days of dynamic perfusion.
“Additionally, Ogiso et al. showed the presence of organ-specific cell–ECM communication that enhanced the maturation of reseeded fetal hepatocytes within decellularized rat livers into both hepatocyte and cholangiocyte lineages, without the addition of any pro-differentiation signals into the culture media during 7 days of dynamic perfusion [217].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [217]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredOgiso et al. reported significantly higher hepatocyte parenchymal engraftment when infused via the biliary tree compared to the portal vein.
“For instance, in a study by Ogiso et al., it was reported that there was significantly higher hepatocytes parenchymal engraftment when infused via the biliary tree compared to the portal vein [217].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [217]
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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-citationUnravelling the memory of the extracellular matrix using MASH-derived decellularized scaffolds
Pinto, G. R., Braz, L. D. G., Pestana, Y., Filho, A. C. D. S., Gomes, M. I. M. D. A. C., de Barros, J. H. O., de Oliveira, T. S., Feng, I. Z. L. F., Santana, B. F., Carvalho, H. F., et al. (2026) · bioRxiv (preprint) · doi:10.64898/2026.03.17.712486
“…cues or “zip codes” direct the behavior of resident and interacting cells, such that homeostatic matrix properties promote normal tissue development and function [13, 14], whereas altered or diseased matrix states drive maladaptive cellular responses and diseased tissue formation [10, 12, 15].”
Horie, H., Fukumitsu, K., Hanabata, Y., Karasuyama, T., Iwaki, K., Munekage, F., Makino, K., Ito, T., Tomofuji, K., Kojima, H., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-39175-2
Self-citation
- Authors
- Ogiso, S., Yasuchika, K., Fukumitsu, K., Ishii, T., Kojima, H., Miyauchi, Y., Yamaoka, R., Komori, J., Katayama, H., Kawai, T., Yoshitoshi, E. Y., Kita, S., Yasuda, K., & Uemoto, S.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Yasuchika, Kentaro
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-10-21
- Volume
- 6
- Issue
- 1
- Pages
- 35887-35887
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5073336
- OpenAlex
- W2536272890
- Cited by
- 59
- References
- 24
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 11 · 2022: 4 · 2021: 12 · 2020: 8 · 2019: 8 · 2018: 2 · 2017: 5
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (16H06903, 15J06001, 15K15065)
- 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
- decellularization, adult hepatocytes, liver regeneration, liver progenitor cells, 3D cell culture
- MeSH terms
- Parenchymal Tissue, Animals, Bile Ducts, Cells, Cultured, Fetus, gamma-Glutamyltransferase, Glucose-6-Phosphatase, Liver, Liver Regeneration, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Rats, Inbred Lew, Transplantation, Heterologous, Cell Culture Techniques, Hepatocytes, Mice, Rats, Keratin-19, Tissue Scaffolds, Transferrins
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