Cell therapy for advanced liver diseases: repair or rebuild
Open accessAbstract
Advanced liver disease presents a significant worldwide health and economic burden and accounts for 3.5% of global mortality. When liver disease progresses to organ failure the only effective treatment is liver transplantation, which necessitates lifelong immunosuppression and carries associated risks. Furthermore, the shortage of suitable donor organs means patients may die waiting for a suitable transplant organ. Cell therapies have made their way from animal studies to a small number of early clinical trials. Herein, we review the current state of cell therapies for liver disease and the mechanisms underpinning their actions (to repair liver tissue or rebuild functional parenchyma). We also discuss cellular therapies that are on the clinical horizon and challenges that must be overcome before routine clinical use is a possibility.
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In myelosuppressive conditions induced by granulocyte colony-stimulating factor, HSPCs proliferate, mobilize, and emigrate rapidly from the bone marrow into peripheral blood, enabling their purification from harvested PB-MNCs based on positive expression of CD34 and CD133 surface markers.
“In myelosuppressive conditions induced by the administration of granulocyte colony-stimulating factor (G-CSF), they proliferate, mobilize, and emigrate rapidly from the BM into PB, thereby enabling their purification from harvested PB-MNCs based on their positive expression of the cluster of differentiation 34 (CD34) and CD133 surface markers [54, 55].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [54]
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Experimental — accuracy not yet measuredMonocytes differentiate into monocyte-derived macrophages and, together with activated Kupffer cells, release pro-inflammatory mediators such as TGF-β and activate hepatic stellate cells, thereby further perpetuating inflammation and promoting fibrosis.
“Among the first recruited circulating immune cells are monocytes, which differentiate into MoMFs and, together with activated KCs, release pro-inflammatory mediators such as TGF-β and activate HSCs, thereby further perpetuating inflammation and promoting fibrosis [9, 54, 78].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [54]
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Experimental — accuracy not yet measuredAntifibrotic cell therapies are usually tested in selected patients with advanced fibrosis and cirrhosis because of technical and logistical requirements.
“Because of the technical and logistical requirements, antifibrotic cell therapies are most often tested in selected patients with advanced fibrosis and cirrhosis.145”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [145]
MSC transfer produced promising antifibrotic effects in mouse models, but human clinical trials with MSCs have had mixed results.
“While MSC transfer led to promising antifibrotic effects in mouse models, clinical trials on MSCs in humans have yielded mixed results.145”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [145]
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References 172 · Cited by 141
- Authors
- Dwyer, B. J., Macmillan, M. T., Brennan, P. N., & Forbes, S. J.
- Affiliations
- MRC Centre for Regenerative Medicine (GB)
- Corresponding author
- Forbes, Stuart J.
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 74
- Issue
- 1
- Pages
- 185-199
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W3088449656
- Cited by
- 141
- References
- 172
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 32 · 2023: 25 · 2022: 23 · 2021: 21
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, cc-by-nc-nd)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust
- Medical Research Council
- UKRMP
- Syncona Ltd
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cell therapy, advanced liver disease, liver regeneration, liver repair, liver transplantation, immunosuppression, organ shortage, clinical trials
- MeSH terms
- Humans, Liver Regeneration, End Stage Liver Disease, Cell- and Tissue-Based Therapy
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