Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation
Open accessAbstract
Background & Aims: and find a way to promote the growth of transplanted hepatocytes. Methods: effects of these compounds on transplanted hepatocytes were then evaluated. Results: , by facilitating HPC conversion. Conclusions: and may facilitate the application of hepatocyte therapy. Impact and implications: and may facilitate the application of hepatocyte therapy.
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ROCK inhibitor Y-27632 and GSK3β inhibitor CHIR99021 reduce actomyosin tension and stabilize β-catenin, creating a proliferative but reversible progenitor-like state.
“Jiang et al. employed ROCK inhibitor Y-27632 and GSK3β inhibitor CHIR99021 to reduce actomyosin tension and stabilize β-catenin, therefore creating a proliferative but reversible progenitor-like state [19].”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [19]
The Results section on reprogramming reports that Y27632 and CHIR99021 produce proliferating hepatic progenitor-like cells, and the Abstract Results says those cells can return to a mature state. The Discussion identifies ROCK inhibition and possible WNT/β-catenin activation, but does not establish that the drugs reduced actomyosin tension or stabilized β-catenin. Page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredFollowing withdrawal into hepatic maturation media, expression of albumin and HNF4A was restored, while levels of alpha-fetoprotein and Ki-67 diminished.
“Following withdrawal into hepatic maturation media, the expression of albumin and HNF4A was restored, although levels of alpha-fetoprotein (AFP) and Ki-67 diminished.”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [19]
Self-assembled microtissues facilitate improved cell-cell interactions and have greater physiological relevance in cell polarity than 2D systems.
“These self-assembled microtissues facilitate improved cell–cell interactions and have greater physiological relevance in cell polarity than 2D systems [19,20,25,26].”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [19]
The Introduction and Results discuss hepatocyte dedifferentiation, proliferation, and culture with small-molecule drugs, but do not address self-assembled microtissues or compare them with 2D systems. Searches for microtissues, cell–cell interactions, and cell polarity found no passage supporting the attributed claim. (LLM, conf=0.74)
Experimental — accuracy not yet measuredSpheroids significantly promote development of bile canaliculi-like networks and maintain stable metabolic zonation, characteristics infrequently preserved in 2D environments.
“Spheroids significantly promote the development of bile canaliculi-like networks and maintain stable metabolic zonation, both of which are characteristics that are infrequently preserved in 2D environments [19].”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [19]
The Results section on reprogramming hepatocytes reports small-molecule-induced proliferation and maturation, not spheroid culture. Searches for spheroids, bile canaliculi, metabolic zonation, and 2D comparisons found no passage in our copy addressing the attributed claim; page numbers were unavailable. (LLM, conf=0.75)
Experimental — accuracy not yet measuredHepatocyte spheroids and organoid-like aggregates are notably robust and reproducible models.
“Within 3D methodologies, hepatocyte spheroids and organoid-like aggregates emerged as notably robust and reproducible models [19,20,25,26].”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [19]
The Introduction and Results discuss chemically induced hepatocyte dedifferentiation and expansion in culture, not hepatocyte spheroids or organoid-like aggregates. Searches for 3D culture, spheroids, organoids, robustness, and reproducibility found no passage in our copy addressing the attributed claim; page numbers were not available. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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Cited by
Sorted by citations
The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances
Kolahdouzmohammadi, M., Tjandra, N., Wu, K., Nikoumaram, R., & Oldani, G. (2026) · Cells · doi:10.3390/cells15161465
“Spheroids significantly promote the development of bile canaliculi-like networks and maintain stable metabolic zonation, both of which are characteristics that are infrequently preserved in 2D environments [19].”
Influential
- Authors
- Jiang, M., Guo, R., Ai, Y., Wang, G., Tang, P., Jia, X., He, B., Yuan, Q., & Xie, X.
- Affiliations
- Chinese Academy of Sciences (CN)
- University of Chinese Academy of Sciences (CN)
- Fudan University (CN)
- Nanchang University (CN)
- Corresponding author
- Xie, Xin
- Venue
- JHEP Reports
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 5
- Issue
- 4
- Pages
- 100670
- ISSN
- 2589-5559 (ISSN-L)
- PMC
- PMC9976449
- OpenAlex
- W4316019742
- Cited by
- 13
- References
- 10
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 4
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- JHEP Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Program of China (2022YFA1104701)
- National Natural Science Foundation of China (32000504, 81730099, 82121005)
- Chinese Academy of Sciences (XDA16010202, XDA16021308)
- Ministry of Science and Technology of the People's Republic of China
- China Postdoctoral Science Foundation (2018M642117)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- hepatocyte repopulation, hepatocyte dedifferentiation, hepatic progenitor cells, small molecule drugs
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