Transplantation of MSCs Overexpressing HGF into a Rat Model of Liver Fibrosis
Abstract
Purpose The aim of this study is to evaluate the effect of overexpressing human hepatocyte growth factor (HGF) for mesenchymal stem cells (MSCs) in liver fibrosis regeneration and magnetic resonance (MR) tracking of MSCs in rat liver. Procedures MSCs were transfected with ad-HGF/ad-green fluorescent protein (GFP) and labeled with superparamagnetic iron oxide (SPIO). The characteristics of SPIO-HGF/MSCs were investigated. Prussian blue staining for iron assessment was conducted in vitro and in vivo. SPIO-HGF/MSCs (group A) or SPIO-GFP/MSCs (group B) were transplanted into a rat model of liver fibrosis, and MR imaging of the rat liver was performed. The signal to noise ratio (SNR) and R2* (1/T2*) value were measured. Prussian blue staining was performed to detect the in vivo distribution of MSCs, and liver Ki67 immunohistochemistry (IHC) staining was studied. The serum levels of HGF, alanine aminotransferase (ALT) and hyaluronic acid (HA) were determined. Results The positive rate of HGF transfection was 93.17 % and the HGF/MSCs were labeled with SPIO successfully (97.80 ± 1.06 %). Labeling of MSCs with SPIO did not alter cell proliferation in vitro. The signal intensity of liver T2* WI images decreased on day 1 after cell transplantation and recovered to pre-transplantation level on day 15 (group A) and day 13 (group B). The SNR of group A were significantly lower than that of group B (P = 0.006), and the R2* values of group A were significantly higher than those of group B (P < 0.001). The R2* value had a significantly negative correlation with SNR. There were more Prussian blue-positive cells in of group A were more than in group B in vivo. The positive rate of Ki67 was 16.11 ± 2.13 %, and the serum level of ALT/HA was decreased in group A. Conclusion HGF transfection improved MSCs localization in the liver and aided liver repair. The R2* value might be a feasible index in addition to SNR to track the SPIO-MSC transplantation in the liver.
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Engineered BM-MSCs overexpressing HGF improve liver regeneration in rat models of disease.
“The engineered BM-MSC to overexpress HGF have also demonstrated promising results in liver [154] and kidney [155] regeneration in rat models of disease.”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [154]
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Liver fibrosis – from bench to bedside
Friedman, S. L. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(02)00429-4 · Cited by 1,780 · see citing works
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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 205 · see citing works
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 · see citing works
- Authors
- Lai, L., Chen, J., Wei, X., Huang, M., Hu, X., Yang, R., Jiang, X., & Shan, H.
- Affiliations
- Guangzhou First People's Hospital (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Sun Yat-sen University (CN)
- Corresponding author
- Jiang, Xinqing
- Shan, Hong
- Venue
- Molecular Imaging and Biology
- Published
- 2015-07-21
- Volume
- 18
- Issue
- 1
- Pages
- 43-51
- ISSN
- 1536-1632 (ISSN-L)
- 1860-2002
- OpenAlex
- W2280997944
- Cited by
- 34
- References
- 1
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 2
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Imaging and Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- mesenchymal stem cells, hepatocyte growth factor, liver fibrosis, superparamagnetic iron oxide labeling, T2 mapping, signal-to-noise ratio, cell transplantation, liver regeneration, Ki-67 cell proliferation, hyaluronic acid, alanine aminotransferase
- MeSH terms
- Adenoviridae, Alanine Transaminase, Animals, Cell Survival, Dextrans, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Genetic Vectors, Humans, Hyaluronic Acid, Immunohistochemistry, Liver Cirrhosis, Magnetic Resonance Imaging, RNA, Messenger, Staining and Labeling, Transfection, Wound Healing, Rats, Sprague-Dawley, Hepatocyte Growth Factor, Ki-67 Antigen, Mesenchymal Stem Cell Transplantation, Cell Proliferation, Green Fluorescent Proteins, Magnetite Nanoparticles, Cell Tracking, Mesenchymal Stem Cells, Real-Time Polymerase Chain Reaction
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