HGF Overexpression in Mesenchymal Stromal Cell-Based Cell Sheets Enhances Autophagy-Dependent Cytoprotection and Proliferation to Guard the Epicardial Mesothelium
Abstract
1. Introduction
2. Results
2.1. Genetically Modified MSCs Form Stable Cell Sheets and Are Characterized by a Prolonged Capacity to Produce HGF
2.2. HGF-MSC CSs Secretome Stimulates c-Met Receptor Phosphorylation and Downstream Signaling in Epicardium Cells
2.3. CSs Transplantation After Infarction Provides Epicardial Cell Recovery and Modulates Autophagy Levels
2.4. HGF-MSC CSs Secretome Protects Epicardial Cells from CoCl2-Induced Death and Stimulates Their Proliferation
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. MSC Isolation and Cultivation
4.3. AAV Purification and MSC Transduction
4.4. CSs Assembly
4.5. ELISA
4.6. Analysis of Extracellular Matrix Proteins and Apoptosis in CSs
4.7. RNA Isolation, Reverse Transcription and Real-Time Quantitative PCR
4.8. Heart Cryoinjury Modeling and Cell Sheet Transplantation
4.9. Flow Cytometry Analysis
4.10. Prestoblue Assay
4.11. Cyto-ID Immunostaining
4.12. Western Blot Analysis
4.13. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene Name | Forward | Reversed |
---|---|---|
Hgf | AACAGGGGCTTTACGTTCACT | CGTCCCTTTATAGCTGCCTCC |
Vegfa | GGAGACTCTTCGAGGAGCACTT | GGCGATTTAGCAGCAGATATAAGAA |
Fgf2 | GCGACCCACACGTCAAACTA | CCGTCCATCTTCCTTCATAGC |
Tgfb1 | TGGAGCAACATGTGGAACTC | GTCAGCAGCCGGTTACCA |
Tgfb2 | TTGTTGCCCTCCTACAGACTGG | GTAAAGAGGGCGAAGGCAGCAA |
Plau | ATGGAAATGGTGACTCTTACCGA | TGG GCA TTG TAG GGT TTC TGA |
Plaur | CGCCACAAACCTCTGCAAC | CTCTGTAGGATAGCGGCATTG |
Serpin1 | TGCAAAAGGTCAGGATCGAGG | ATGAAGAGGATTGTCTCTGTCGG |
Fn1 | GGAATGGACCTGCAAACCTA | GTAGGGCTTTTCCCAGGTCT |
Col1a1 | CCGCTGGTCAAGATGGTC | CTCCAGCCTTTCCAGGTTCT |
Col3a1 | CTGTAACATGGAAACTGGGGAAA | CCATAGCTGAACTGAAAACCACC |
Col4a1 | CTGGCACAAAAGGGACGAG | ACGTGGCCGAGAATTTCACC |
Actb | GGCTGTATTCCCCTCCATCG | CCAGTTGGTAACAATGCCATGT |
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Dergilev, K.; Beloglazova, I.; Tsokolaeva, Z.; Azimova, E.; Dolgodvorova, A.; Goltseva, Y.; Boldyreva, M.; Menshikov, M.; Penkov, D.; Parfyonova, Y. HGF Overexpression in Mesenchymal Stromal Cell-Based Cell Sheets Enhances Autophagy-Dependent Cytoprotection and Proliferation to Guard the Epicardial Mesothelium. Int. J. Mol. Sci. 2025, 26, 7298. https://doi.org/10.3390/ijms26157298
Dergilev K, Beloglazova I, Tsokolaeva Z, Azimova E, Dolgodvorova A, Goltseva Y, Boldyreva M, Menshikov M, Penkov D, Parfyonova Y. HGF Overexpression in Mesenchymal Stromal Cell-Based Cell Sheets Enhances Autophagy-Dependent Cytoprotection and Proliferation to Guard the Epicardial Mesothelium. International Journal of Molecular Sciences. 2025; 26(15):7298. https://doi.org/10.3390/ijms26157298
Chicago/Turabian StyleDergilev, Konstantin, Irina Beloglazova, Zoya Tsokolaeva, Ekaterina Azimova, Aleria Dolgodvorova, Yulia Goltseva, Maria Boldyreva, Mikhail Menshikov, Dmitry Penkov, and Yelena Parfyonova. 2025. "HGF Overexpression in Mesenchymal Stromal Cell-Based Cell Sheets Enhances Autophagy-Dependent Cytoprotection and Proliferation to Guard the Epicardial Mesothelium" International Journal of Molecular Sciences 26, no. 15: 7298. https://doi.org/10.3390/ijms26157298
APA StyleDergilev, K., Beloglazova, I., Tsokolaeva, Z., Azimova, E., Dolgodvorova, A., Goltseva, Y., Boldyreva, M., Menshikov, M., Penkov, D., & Parfyonova, Y. (2025). HGF Overexpression in Mesenchymal Stromal Cell-Based Cell Sheets Enhances Autophagy-Dependent Cytoprotection and Proliferation to Guard the Epicardial Mesothelium. International Journal of Molecular Sciences, 26(15), 7298. https://doi.org/10.3390/ijms26157298