Conversion of terminally committed hepatocytes to culturable bipotent progenitor cells with regenerative capacity
Open accessAbstract
A challenge for advancing approaches to liver regeneration is loss of functional differentiation capacity when hepatocyte progenitors are maintained in culture. Recent lineage-tracing studies have shown that mature hepatocytes (MHs) convert to an immature state during chronic liver injury, and we investigated whether this conversion could be recapitulated in vitro and whether such converted cells could represent a source of expandable hepatocytes. We report that a cocktail of small molecules, Y-27632, A-83-01, and CHIR99021, can convert rat and mouse MHs in vitro into proliferative bipotent cells, which we term chemically induced liver progenitors (CLiPs). CLiPs can differentiate into both MHs and biliary epithelial cells that can form functional ductal structures. CLiPs in long-term culture did not lose their proliferative capacity or their hepatic differentiation ability, and rat CLiPs were shown to extensively repopulate chronically injured liver tissue. Thus, our study advances the goals of liver regenerative medicine.
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Two recent studies have demonstrated the generation of expandable progenitor-like cells and duct-like cells from rodent hepatocytes in vitro.
“Two recent studies have respectively demonstrated the generation of expandable progenitor-like cells and duct-like cells from rodent hepatocytes in vitro (Katsuda et al., 2017; Wu et al., 2017”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Katsuda et al., 2017
The rodent hepatocyte medium containing Y-27632, A-83-01, and CHIR99021 (YAC) was reported to induce the proliferation of rodent hepatocytes.
“the rodent hepatocyte medium containing Y-27632, A-83-01, and CHIR99021 (YAC) medium, which was reported to induce the proliferation of rodent hepatocytes (Katsuda et al., 2017”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Katsuda et al., 2017
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- Authors
- Katsuda, T., Kawamata, M., Hagiwara, K., Takahashi, R.-U., Yamamoto, Y., Camargo, F. D., & Ochiya, T.
- Affiliations
- National Cancer Center Research Institute (JP)
- Boston Children's Hospital (US)
- National Cancer Centre Japan (JP)
- Corresponding author
- Ochiya, Takahiro
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 20
- Issue
- 1
- Pages
- 41-55
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2553349418
- Cited by
- 260
- References
- 6
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 36 · 2023: 22 · 2022: 30 · 2021: 41 · 2020: 36 · 2019: 20 · 2018: 31 · 2017: 11
- FWCI
- 14.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- Y-27632, CHIR99021, liver regeneration, chronic liver injury, hepatocyte repopulation, lineage tracing
- MeSH terms
- Amides, Animals, Cell Differentiation, Cells, Cultured, Chimera, Diploidy, Epithelial Cells, Liver, Liver Regeneration, Pyrazoles, Pyridines, Pyrimidines, Regeneration, Stem Cells, Thiosemicarbazones, Time Factors, Reproducibility of Results, Cell Lineage, Hepatocytes, Cell Proliferation, Mice, Rats, Small Molecule Libraries, Cellular Reprogramming
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