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Human umbilical cord mesenchymal stem cells inhibit proliferation of hepatic stellate cells in vitro
Open accessAbstract
The effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on the proliferation of hepatic stellate cells (HSCs) is largely unknown. The purpose of this study was to explore the mechanism of action of hUC‑MSCs on the proliferation of HSCs in vitro. The upper and lower double-cell co-culture system was established between hUC‑MSCs and HSCs in the experimental group. HSCs were cultured alone as a negative control group. Cell proliferation and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Cell supernatants were harvested to determine the concentration of transforming growth factor-β1 (TGF-β1) by ELISA. mRNA and protein of TGF-β1, Smad3 and Smad7 in HSCs were determined by reverse transcription-polymerase chain reaction and western blotting, respectively. In the co-culture group, the proliferation of HSCs was significantly inhibited compared with the negative control group at 24 and 48 h (p<0.05). Apoptosis of HSCs in the co-culture group increased compared with that in the negative control group, which was more obvious at 48 h (p<0.05). The concentration of TGF-β1 in the co-culture group was significantly lower than in the HSCs cultured alone (p<0.05). After HSCs were co-cultured with hUC‑MSCs for 48 h, expression of TGF-β1 and Smad3 mRNA and protein was reduced and expression of Smad7 mRNA and protein was increased compared with the negative control group (p<0.05). hUC‑MSCs inhibited proliferation of HSCs, possibly through inhibiting TGF-β1 and Smad3 expression and increasing Smad7 protein expression.
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UC-MSCs impair HSC proliferation by inhibiting the expression of TGFβ-1 and Smad3 and increasing the expression of Smad7.
“Zhang et al. reported that UC-MSCs impair HSC proliferation by inhibiting the expression of TGFβ-1 and Smad3 and increasing the expression of Smad7 [186].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [186]
The Abstract and Results report inhibited HSC proliferation, reduced TGF-β1 and Smad3 expression, and increased Smad7 expression in co-culture. The Abstract describes the proposed mechanism as occurring “possibly through” those expression changes, whereas the citing sentence states that causal mechanism without qualification. (LLM, conf=0.84)
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- Volarevic, 2014, Concise review: Therapeutic potential of mesenchymal stem cells for the treatment of acute liver failure and cirrhosis, Stem Cells, 32, 2818, 10.1002/stem.1818 · DOI
- Berardis, 2015, Use of mesenchymal stem cells to treat liver fibrosis: Current situation and future prospects, World J Gastroenterol, 21, 742, 10.3748/wjg.v21.i3.742 · DOI
- Zhang, 2012, Research on stem cells as candidates to be differentiated into hepatocytes, Biomed Mater Eng, 22, 105
- Secunda, 2015, Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: A comparative study, Cytotechnology, 67, 793, 10.1007/s10616-014-9718-z · DOI
- Berardis, 2014, Gene expression profiling and secretome analysis differentiate adult-derived human liver stem/progenitor cells and human hepatic stellate cells, PLoS One, 9, e86137, 10.1371/journal.pone.0086137 · DOI
- Pan, 2011, Delta-like 1 serves as a new target and contributor to liver fibrosis down-regulated by mesenchymal stem cell transplantation, J Biol Chem, 286, 12340, 10.1074/jbc.M110.194498 · DOI
- Burra, 2012, Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury, BMC Gastroenterol, 12, 88, 10.1186/1471-230X-12-88 · DOI
- Sakaida, 2004, Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice, Hepatology, 40, 1304, 10.1002/hep.20452 · DOI
- Li, 2013, Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis, Stem Cells Dev, 22, 845, 10.1089/scd.2012.0395 · DOI
- Eom, 2015, Mesenchymal stem cell therapy for liver fibrosis, Korean J Intern Med, 30, 580, 10.3904/kjim.2015.30.5.580 · DOI · Paper page
- Zhang, 2015, Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway, Mol Med Rep, 12, 7227, 10.3892/mmr.2015.4362 · DOI
- Røsland, 2009, Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation, Cancer Res, 69, 5331, 10.1158/0008-5472.CAN-08-4630 · DOI
- Tang, 2013, Malignant transformation potentials of human umbilical cord mesenchymal stem cells both spontaneously and via 3-methycholanthrene induction, PLoS One, 8, e81844, 10.1371/journal.pone.0081844 · DOI
- Wang, 2016, Liver-derived human mesenchymal stem cells: A novel therapeutic source for liver diseases, Stem Cell Res Ther, 7, 71, 10.1186/s13287-016-0330-3 · DOI
- Kim, 2005, Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to resolution from liver cirrhosis, Am J Pathol, 166, 1017, 10.1016/S0002-9440(10)62323-1 · DOI
- Zhao, 2016, Epithelial-mesenchymal transition in liver fibrosis, Biomed Rep, 4, 269, 10.3892/br.2016.578 · DOI
- Borkham-Kamphorst, 2004, Dominant-negative soluble PDGF-beta receptor inhibits hepatic stellate cell activation and attenuates liver fibrosis, Lab Invest, 84, 766, 10.1038/labinvest.3700094 · DOI
- Saxena, 2004, Leptin as a novel profibrogenic cytokine in hepatic stellate cells: Mitogenesis and inhibition of apoptosis mediated by extracellular regulated kinase (Erk) and Akt phosphorylation, FASEB J, 18, 1612, 10.1096/fj.04-1847fje · DOI
- Lang, 2004, Leptin facilitates proliferation of hepatic stellate cells through up-regulation of platelet-derived growth factor receptor, Biochem Biophys Res Commun, 323, 1091, 10.1016/j.bbrc.2004.08.192 · DOI
- Hata, 2016, TGF-β signaling from receptors to Smads, Cold Spring Harb Perspect Biol, 8, a022061, 10.1101/cshperspect.a022061 · DOI
- Argentou, 2016, TGF-β signaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment, Inflamm Res, 65, 355, 10.1007/s00011-016-0921-6 · DOI
- Lu, 2009, Correlations of TGF-betaRII, Smad4 and Smad7 expression to clinicopathologic characteristics and prognosis of gastric cancer, Ai Zheng, 28, 538
Cited by
Sorted by citations
Mesenchymal stromal cells in hepatic fibrosis/cirrhosis: from pathogenesis to treatment
Yang, X., Li, Q., Liu, W., Zong, C., Wei, L., Shi, Y., & Han, Z. (2023) · Cellular & Molecular Immunology · doi:10.1038/s41423-023-00983-5 · Cited by 120
Pan, X., Gao, T., & Wang, B. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01520-9 · Cited by 2
Metadata
- Authors
- Zhang, L.-T., Peng, X.-B., Fang, X.-Q., Li, J.-F., Chen, H., & Mao, X.-R.
- Affiliations
- Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
- Baoji City Central Hospital (CN)
- First Hospital of Lanzhou University (CN)
- ORCID
- Chen, Hong
- Venue
- International Journal of Molecular Medicine
- Publisher
- Spandidos Publications
- Published
- 2018-02-16
- Volume
- 41
- Issue
- 5
- Pages
- 2545-2552
- ISSN
- 1107-3756 (ISSN-L)
- 1791-244X
- PMC
- PMC5846650
- OpenAlex
- W2793766128
- Cited by
- 29
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 3
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- International Journal of Molecular Medicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lanzhou University Institutional Repository (submittedVersion)
- Funders
- Natural Science Foundation of Gansu Province
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- human umbilical cord mesenchymal stem cells, hepatic stellate cells, cell proliferation, apoptosis, TGF-β1, Smad3, Smad7, co-culture, liver fibrosis
- MeSH terms
- Cell Line, Gene Expression Regulation, Humans, Umbilical Cord, Apoptosis, Coculture Techniques, Cell Proliferation, Smad3 Protein, Smad7 Protein, Transforming Growth Factor beta1, Hepatic Stellate Cells, Mesenchymal Stem Cells
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