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Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure
Open accessAbstract
BACKGROUND: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has emerged as a novel therapy for acute liver failure (ALF). However, the homing efficiency of BMSCs to the injured liver sites appears to be poor. In this study, we aimed to determine if overexpression of c-Met in BMSCs could promote the homing ability of BMSCs to rat livers affected by ALF. METHODS: Overexpression of c-Met in BMSCs (c-Met-BMSCs) was attained by transfection of naive BMSCs with the lenti-c-Met-GFP. The impact of transplanted c-Met-BMSCs on both homing and repair of ALF was evaluated and compared with lenti-GFP empty vector transfected BMSCs (control BMSCs). RESULTS: After cells were transfected with the lenti-c-Met-GFP vector, the BMSCs displayed very high expression of c-Met protein as demonstrated by Western blot. In addition, in vitro transwell migration assays showed that the migration ability of c-Met-BMSCs was significantly increased in comparison with that of control BMSCs (P < 0.05), and was dependent on hepatocyte growth factor (HGF). Furthermore, rats with ALF that received transplanted c-Met-BMSCs showed significantly improved homing ability to the injured liver; this was accompanied by elevated survival rates and liver function in the ALF rats. Parallel pathological examination further confirmed that transplantation of c-Met-BMSCs ameliorated liver injury with reduced hepatic activity index (HAI) scores, and that the effects of c-Met-BMSCs were more profound than those of control BMSCs. CONCLUSIONS: Overexpression of c-Met promotes the homing of BMSCs to injured hepatic sites in a rat model of ALF, thereby improving the efficacy of BMSC therapy for ALF repair.
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MSC overexpression with c-met and CXCR4 improves homing to the livers of acute liver failure rodent models.
“Regarding liver diseases, MSC overexpression with c-met and CXCR4 improved homing to the livers of acute liver failure rodent models [156], [157], resulting in enhanced liver function and increased survival rates.”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [156]
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Sorted by citations
Mesenchymal stem cell secretome for regenerative medicine: Where do we stand?
Trigo, C. M., Rodrigues, J. S., Camões, S. P., Solá, S., & Miranda, J. P. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2024.05.004 · Cited by 252
“Regarding liver diseases, MSC overexpression with c-met and CXCR4 improved homing to the livers of acute liver failure rodent models [156,157], resulting in enhanced liver function and increased survival rates.”
Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease
Yuan, M., Hu, X., Yao, L., Jiang, Y., & Li, L. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02858-4 · Cited by 89
He, L., Xu, J., Huang, P., Bai, Y., Chen, H., Xu, X., Hu, Y., Liu, J., & Zhang, H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137235 · Cited by 8
Metadata
- Authors
- Wang, K., Li, Y., Zhu, T., Zhang, Y., Li, W., Lin, W., Li, J., & Zhu, C.
- Affiliations
- Anhui Medical University (CN)
- Jiangsu Province Hospital (CN)
- Harvard University (US)
- Corresponding author
- Zhu, Chuanlong
- Venue
- Stem Cell Research & Therapy
- Published
- 2017-07-05
- Volume
- 8
- Issue
- 1
- Pages
- 162-162
- ISSN
- 1757-6512 (ISSN-L)
- PMC
- PMC5499016
- OpenAlex
- W2730810791
- Cited by
- 54
- References
- 1
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 13 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 5
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Stem Cell Research & Therapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81271713)
- the Gilead Sciences Research Scholars Program in Liver Disease – Asia
- the Key Medical Talents Fund of Jiangsu Province.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- c-Met, bone marrow mesenchymal stem cells, acute liver failure, stem cell homing, hepatocyte growth factor, cell migration, liver regeneration, stem cell transplantation, gene overexpression
- MeSH terms
- Animals, Bone Marrow Cells, Disease Models, Animal, Liver, Male, Transduction, Genetic, Lentivirus, Liver Failure, Acute, Rats, Sprague-Dawley, Proto-Oncogene Proteins c-met, Mesenchymal Stem Cell Transplantation, Rats, Mesenchymal Stem Cells
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