Assessing the therapeutic potential of lab-made hepatocytes
Open accessAbstract
Hepatocyte transplantation has potential as a bridge or even alternative to whole‐organ liver transplantation. Because donor livers are scarce, realizing this potential requires the development of alternative cell sources. To be therapeutically effective, surrogate hepatocytes must replicate the complex function and ability to proliferate of primary human hepatocytes. Ideally, they are also autologous to eliminate the need for immune suppression, which can have severe side effects and may not be sufficient to prevent rejection long term. In the past decade, several methods have been developed to generate hepatocytes from other readily and safely accessible somatic cells. These lab‐made hepatocytes show promise in animal models of liver diseases, supporting the feasibility of autologous liver cell therapies. Here, we review recent preclinical studies exemplifying different types of lab‐made hepatocytes that can potentially be used in autologous liver cell therapies. To define the therapeutic efficacy of current lab‐made hepatocytes, we compare them to primary human hepatocytes, focusing on engraftment efficiency and posttransplant proliferation and function. In addition to summarizing published results, we discuss animal models and assays effective in assessing therapeutic efficacy. This analysis underscores the therapeutic potential of current lab‐made hepatocytes, but also highlights deficiencies and uncertainties that need to be addressed in future studies aimed at developing liver cell therapies with lab‐made hepatocytes. (H epatology 2016;64:287–294)
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The repopulation efficiency of HLCs is around 2%, far lower than that of PHHs, which is around 70%.
“The repopulation efficiency of HLCs, which is around 2%, is far lower than that of PHHs, which is around 70% (Ji et al., 2013; Rezvani et al., 2016; Sampaziotis et al., 2015”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Rezvani et al., 2016
The ‘Therapeutic efficacy of current lab-made hepatocytes’ section says lab-made hepatocytes generally repopulate injured mouse livers less effectively than primary human hepatocytes. Its iMPC-Heps subsection reports 2% repopulation for one lab-made cell type, but the iPSC-Heps subsection reports up to 20%; the copy does not establish 2% as a general figure or give the claimed 70% figure for primary hepatocytes. Page numbers were not available in the indexed passages. (LLM, conf=0.88)
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Scholz, J. A. C., Cuellar, C. A., VanLith, C. J., la Vega, R. E. D., Boschen, S. L., Evans, C. H., & Hickey, R. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814338-4.00030-1 · Cited by 2 · see citing works
Cell therapy for liver diseases: From hepatocyte transplantation to bioartificial livers
Yuan, X., Sun, Z., Wu, J., Hui, L., & Zhang, L. (2024) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2024.100530 · Cited by 2 · see citing works
Yang, T., Zhu, X., Long, M., Hui, L., Yuan, X., Sun, Z., Zhang, L., Xia, Q., & Wan, P. (2025) · BMJ Open · doi:10.1136/bmjopen-2024-087828 · Cited by 1 · see citing works
Liver Capsule: Multipotent stem cells and their lineage restriction to hepatocytes
Duncan, S. A. (2016) · Hepatology · doi:10.1002/hep.28727 · Cited by 1 · see citing works
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The Bioengineering of Exogenic Organs and/or Cells for Use in Regenerative Medicine
Aravalli, R. N., Shiao, M. L., Lu, W.-C., Xie, H. M., Pearce, C., Toman, N. G., Danczyk, G., Sipe, C. J., Miller, Z. D., Crane, A. T., et al. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813068-1.00015-4 · Cited by 1 · see citing works
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Modelling and genetic correction of liver genetic diseases
Zabulica, M. (2021) · Figshare
Hidaka, M., Miyamoto, D., & Eguchi, S. (2023) · Springer eBooks · doi:10.1007/978-981-99-0846-2_21-1
Hidaka, M., Miyamoto, D., & Eguchi, S. (2024) · Springer eBooks · doi:10.1007/978-981-99-7119-0_21
Biliary tree stem cell transplantation
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- Authors
- Rezvani, M., Grimm, A. A., & Willenbring, H.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Willenbring, Holger
- Venue
- Hepatology
- Published
- 2016-05-26
- Volume
- 64
- Issue
- 1
- Pages
- 287-294
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC5316561
- OpenAlex
- W2311496492
- Cited by
- 54
- References
- 39
- Citations by year
- 2025: 5 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 6
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R21AA022158)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK026743, T32DK007762)
- Liver Center, University of California, San Francisco (UH3 NS080691, P30 DK26743, R21 AA022158)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- hepatocyte transplantation, primary human hepatocytes, treatment efficacy assessment, alternative cell sources, liver transplantation alternatives
- MeSH terms
- Animals, Humans, Hepatocytes, Cell- and Tissue-Based Therapy
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