Mesenchymal stromal cells in hepatic fibrosis/cirrhosis: from pathogenesis to treatment
Open accessAbstract
Hepatic fibrosis/cirrhosis is a significant health burden worldwide, resulting in liver failure or hepatocellular carcinoma (HCC) and accounting for many deaths each year. The pathogenesis of hepatic fibrosis/cirrhosis is very complex, which makes treatment challenging. Endogenous mesenchymal stromal cells (MSCs) have been shown to play pivotal roles in the pathogenesis of hepatic fibrosis. Paradoxically, exogenous MSCs have also been used in clinical trials for liver cirrhosis, and their effectiveness has been observed in most completed clinical trials. There are still many issues to be resolved to promote the use of MSCs in the clinic in the future. In this review, we will examine the controversial role of MSCs in the pathogenesis and treatment of hepatic fibrosis/cirrhosis. We also investigated the clinical trials involving MSCs in liver cirrhosis, summarized the parameters that need to be standardized, and discussed how to promote the use of MSCs from a clinical perspective.
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MSCs vary in morphology, tri-lineage differentiation potential, proliferation rates, and immunomodulatory properties across different donors, tissue sources, subpopulations, and individual cells, referred to as heterogeneity.
“Of note, MSCs vary in morphology, tri-lineage differentiation potential, proliferation rates, and immunomodulatory properties across different donors, tissue sources, subpopulations, and individual cells, referred to as heterogeneity [178, 308–310].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [178]
The Cell preparation section says MSC heterogeneity arises from donor, tissue source, and natural subpopulation diversity, and that heterogeneous cells differ in proliferation, differentiation, and immunoregulatory capacities. It does not specifically establish variation in morphology or tri-lineage differentiation potential, or describe differences between individual cells. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA variety of genes, including HGF, FGF, IGF1, HNF4α, PRL, IL-10, Smad7, CXCR2, MMP13, and ECM1, have been overexpressed in MSCs.
“A variety of genes have been overexpressed in MSCs, such as HGF, FGF, IGF1, HNF4α, phosphatase of regenerating liver-1 (PRL), IL-10, Smad7, CXCR2, MMP13, and ECM1 [178, 194, 253, 361–363].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [178]
The “Gene modification of MSCs” section (page unavailable) says HGF was overexpressed and lists IGF1, HNF4α, FGF4/FGF21, IL-10, PTP4A1 (PRL-1), SMAD7, and ECM1 as genes used to modify MSCs. It does not report CXCR2 or MMP13 overexpression in MSCs; the separate mention of MMP-13 concerns reduced enzyme activity after MSC treatment in cardiac fibrosis. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAmong all routes, intravenous administration via the peripheral vein is the most noninvasive, convenient, economical, and safe, allowing for MSC-host cell interactions and multiple infusions, yet experimental studies and commentary on its usage are conflicting.
“Among all routes, intravenous administration via the peripheral vein is the most noninvasive, convenient, economical, and safe, allowing for MSC-host cell interactions and multiple infusions, yet experimental studies and commentary on its usage are conflicting [178, 293].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [178]
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Experimental — accuracy not yet measuredTransplant waiting lists are growing faster than donor availability, and long-term outcomes are complicated by rejection and immunosuppression.
“Yet, with transplant waiting lists growing faster than donor availability, and long-term outcomes still complicated by rejection and immunosuppression, it's clear we need better alternatives [[3], [4], [5]].”
From From scaffold to function: A systematic review on dLECM-based hydrogels for liver tissue engineering — Fabrication, properties, and translational applications (2026) · cites this paper as [3]
The Introduction (page unavailable) says liver transplantation can take a long time because a suitable organ must be found, and presents MSCs as an alternative. It does not say waiting lists are growing faster than donor availability or that long-term liver-transplant outcomes are complicated by rejection and immunosuppression. The rejection discussed under “Cell-free therapy based on MSCs” concerns MSC-based therapies, not liver transplants. (LLM, conf=0.85)
Experimental — accuracy not yet measuredConventional MSC cultures rely on fetal bovine serum (FBS), which is limited by batch-to-batch variability and potential hazards, including pathogen contamination, transmission of xenogeneic diseases, and risk of immune rejection.
“Conventional MSC cultures rely on fetal bovine serum (FBS) to supply essential nutrients and growth factors for cell development, which is limited by batch-to-batch variability and potential hazards, including pathogen contamination, transmission of xenogeneic diseases, as well as the risk of immune rejection [178, 324].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [178]
Liver transplantation remains the only definitive cure for end-stage liver disease.
“For patients with end-stage disease, liver transplantation remains the only definitive cure.”
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References 260 · Cited by 120
Research works printed but not linked: 7
- [142]142. Cho JW, Lee CY, Ko Y. Therapeutic potential of mesenchymal stem cells over- expressing human forkhead box A2 gene in the regeneration of damaged liver tissues. J Gastroenterol Hepatol. 2012;27:1362-70.
- [247]247. Lai L, Chen J, Wei X, Huang M, Hu X, Yang R, et al. Transplantation of MSCs Overexpressing HGF into a Rat Model of Liver Fibrosis. Mol Imaging Biol. 2016;18:43-51.
- [248]248. Seo K-W, Sohn S-Y, Bhang D-H, Nam M-J, Lee H-W, Youn H-Y. Therapeutic effects of hepatocyte growth factor-overexpressing human umbilical cord blood- derived mesenchymal stem cells on liver fibrosis in rats. Cell Biol Int. 2014;38:106-16.
- [249]249. Moon SH, Lee CM, Park S-H, Jin Nam M. Effects of hepatocyte growth factor gene-transfected mesenchymal stem cells on dimethylnitrosamine-induced liver fibrosis in rats. Growth Factors. 2019;37:105-19.
- [250]250. Kim M-D, Kim S-S, Cha H-Y, Jang S-H, Chang D-Y, Kim W, et al. Therapeutic effect of hepatocyte growth factor-secreting mesenchymal stem cells in a rat model of liver fibrosis. Exp Mol Med. 2014;46:e110-e110.
- [253]253. Ye Z, Lu W, Liang L, Tang M, Wang Y, Li Z, et al. Mesenchymal stem cells overexpressing hepatocyte nuclear factor-4 alpha alleviate liver injury by modulating anti-inflammatory functions in mice. Stem Cell Research & Therapy. 2019;10:149.
- [257]257. Choi JS, Jeong IS, Han JH, Cheon SH, Kim S-W. IL-10-secreting human MSCs generated by TALEN gene editing ameliorate liver fibrosis through enhanced anti-fibrotic activity. Biomater Sci. 2019;7:1078-87.
- Authors
- Yang, X., Li, Q., Liu, W., Zong, C., Wei, L., Shi, Y., & Han, Z.
- Affiliations
- University of Rome Tor Vergata (IT)
- Shanghai Institute of Nutrition and Health (CN)
- Second Military Medical University (CN)
- Corresponding author
- Shi, Yufang
- Han, Zhipeng
- Venue
- Cellular & Molecular Immunology
- Published
- 2023-02-24
- Volume
- 20
- Issue
- 6
- Pages
- 583-599
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC10229624
- OpenAlex
- W4321748211
- Cited by
- 120
- References
- 260
- Citations by year
- 2026: 32 · 2025: 50 · 2024: 29 · 2023: 9
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-05-15)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- PubMed Central (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82073037)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- mesenchymal stem cells, liver fibrosis, liver cirrhosis, fibrosis pathogenesis, clinical trials, hepatocellular carcinoma, liver failure
- MeSH terms
- Fibrosis, Carcinoma, Hepatocellular, Humans, Liver Cirrhosis, Liver Neoplasms, Mesenchymal Stem Cell Transplantation, Hepatic Stellate Cells, Mesenchymal Stem Cells
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