Beneficial Effect of Mechanical Stimulation on the Regenerative Potential of Muscle-Derived Stem Cells Is Lost by Inhibiting Vascular Endothelial Growth Factor
| Autor: | Jonathan D. Proto, Bing Wang, Sarah A. Beckman, Johnny Huard, William C.W. Chen, Logan R Mlakar, Ying Tang |
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| Rok vydání: | 2013 |
| Předmět: |
Vascular Endothelial Growth Factor A
Angiogenesis Neovascularization Physiologic Mice Transgenic Stimulation Mice SCID Biology Article Dystrophin Small hairpin RNA Mice chemistry.chemical_compound Cell Movement Cell Adhesion Animals Regeneration Myocyte RNA Small Interfering Muscle Skeletal Vascular Endothelial Growth Factor Receptor-1 Stem Cells Regeneration (biology) Graft Survival Cell Differentiation Muscular Dystrophy Animal Cell biology Muscular Dystrophy Duchenne Transplantation Vascular endothelial growth factor Disease Models Animal Lac Operon chemistry Immunology Mice Inbred mdx Stress Mechanical Stem cell Cardiology and Cardiovascular Medicine Stem Cell Transplantation |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 33:2004-2012 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.112.301166 |
| Popis: | Objective— We previously reported that mechanical stimulation increased the effectiveness of muscle-derived stem cells (MDSCs) for tissue repair. The objective of this study was to determine the importance of vascular endothelial growth factor (VEGF) on mechanically stimulated MDSCs in a murine model of muscle regeneration. Approach and Results— MDSCs were transduced with retroviral vectors encoding the LacZ reporter gene (lacZ-MDSCs), the soluble VEGF receptor Flt1 (sFlt1-MDSCs), or a short hairpin RNA (shRNA) targeting messenger RNA of VEGF (shRNA_VEGF MDSCs). Cells were subjected to 24 hours of mechanical cyclic strain and immediately transplanted into the gastrocnemius muscles of mdx/scid mice. Two weeks after transplantation, angiogenesis, fibrosis, and regeneration were analyzed. There was an increase in angiogenesis in the muscles transplanted with mechanically stimulated lacZ-MDSCs compared with nonstimulated lacZ-MDSCs, sFlt1-MDSCs, and shRNA _VEGF MDSCs. Dystrophin-positive myofiber regeneration was significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. In vitro proliferation of MDSCs was not decreased by inhibition of VEGF; however, differentiation into myotubes and adhesion to collagen were significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. Conclusions— The beneficial effects of mechanical stimulation on MDSC-mediated muscle repair are lost by inhibiting VEGF. |
| Databáze: | OpenAIRE |
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