HDAC inhibitors support long-term expansion of porcine hepatocytes in vitro
Open accessAbstract
Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have garnered attention as a potential alternative source. Nonetheless, traditional primary porcine hepatocytes exhibit certain limitations in function maintenance and in vitro proliferation. This study has discovered that by using histone deacetylase inhibitors (HDACi), primary porcine hepatocytes can be successfully reprogrammed into liver progenitor cells with high proliferative potential. This method enables porcine hepatocytes to proliferate over an extended period in vitro and exhibit increased susceptibility in lentivirus-mediated gene modification. These liver progenitor cells can readily differentiate into mature hepatocytes and, upon microencapsulation transplantation into mice with acute liver failure, significantly improve the survival rate. This research provides new possibilities for the application of porcine hepatocytes in the treatment of end-stage liver disease.
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Three-dimensional culture platforms generally improve hepatocyte maturation and functional stability but are often not scalable due to matrix dependence, technical complexity, handling requirements, and cost.
“Finally, three-dimensional (3D) culture platforms generally improve hepatocyte maturation and functional stability, but these are often not scalable due to matrix dependence, technical complexity, handling requirements, and cost.”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [21]
Valproic acid induces chromatin relaxation in primary hepatocytes, facilitating long-term, karyotypically stable development, effective gene modification, and therapeutic restoration following microencapsulated transplantation.
“The use of valproic acid induces chromatin relaxation in PHs, facilitating long-term, karyotypically stable development, effective gene modification, and therapeutic restoration following microencapsulated transplantation [21].”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [21]
3D culture systems suffer poor scalability, non-specific adsorption of small molecules onto scaffold materials, technical complexity, and large batch-to-batch variability of ECM components, impairing reproducibility.
“Often, the problems cited are poor scalability, non-specific adsorption of SMs onto scaffold materials, technical complexity, and the large batch-to-batch variability of ECM components, impairing reproducibility [21].”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [21]
3D culture systems are consistently superior to conventional monolayer cultures in hepatocyte functionality and viability.
“Although these systems have shown to be consistently superior to conventional monolayer cultures in terms of hepatocyte functionality and viability, they suffer from intrinsic limitations.”
From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [21]
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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
“Often, the problems cited are poor scalability, non-specific adsorption of SMs onto scaffold materials, technical complexity, and the large batch-to-batch variability of ECM components, impairing reproducibility [21].”
Zhou, Y., Zeng, M., Fu, G., & Gao, Y. (2026) · Stem Cell Reviews and Reports · doi:10.1007/s12015-026-11172-y
Self-citation
- Authors
- Li, G., Zeng, M., Yan, Z., Cai, S., Ma, Y., Wang, Y., Li, S., Li, Y., Zhong, K., Xiao, M., Fu, G., Weng, J., & Gao, Y.
- Affiliations
- Zhujiang Hospital (CN)
- Wenzhou Medical University (CN)
- Nanjing General Hospital of Nanjing Military Command (CN)
- Sun Yat-sen University Cancer Center (CN)
- Corresponding author
- Xiao, Mingjia
- Fu, Gongbo
- Weng, Jun
- Gao, Yi
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2024-08
- Volume
- 177
- Pages
- 116973
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W4399886638
- Cited by
- 2
- References
- 61
- Citations by year
- 2026: 2
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Key Research and Development Program of China (2022YFA1104900)
- China Postdoctoral Science Foundation (2021MD703958)
- National Natural Science Foundation of China (82002591, 82200703, 31972926)
- Basic and Applied Basic Research Foundation of Guangdong Province (2021A1515110228)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- porcine hepatocytes, histone deacetylase inhibitors, valproic acid, liver progenitor cells, hepatocyte expansion, microencapsulation, acute liver failure, end-stage liver disease, hepatocyte transplantation, hepatocyte differentiation
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Stem Cells, Swine, Hepatocytes, Cell Proliferation, Mice, Histone Deacetylase Inhibitors
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