Synergistic effect of vascular endothelial growth factor and granulocyte colony-stimulating factor double gene therapy in mouse limb ischemia
| Autor: | Radovan Borojevic, Chester Bittencourt Sacramento, Ruy R. Campos, José Carlos Costa Baptista-Silva, Flávia Helena da Silva, Sang Won Han, Eduardo Gallatti Yasumura, Hamilton Silva Junior, Nance Beyer Nardi, Abram Beutel, Vivian Yochiko Samoto, Jane Zveiter de Moraes |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty Necrosis Angiogenesis Genetic enhancement Neovascularization Physiologic Granulocyte Biology Mice chemistry.chemical_compound Ischemia Fibrosis Internal medicine Granulocyte Colony-Stimulating Factor Drug Discovery Genetics medicine Animals Regeneration Muscle Skeletal Molecular Biology Genetics (clinical) Peripheral Vascular Diseases Mice Inbred BALB C Extremities Genetic Therapy medicine.disease Granulocyte colony-stimulating factor Vascular endothelial growth factor Endocrinology medicine.anatomical_structure chemistry Immunology Molecular Medicine medicine.symptom Stem cell |
| Zdroj: | The Journal of Gene Medicine. |
| ISSN: | 1521-2254 1099-498X |
| DOI: | 10.1002/jgm.1434 |
| Popis: | Background Vascular endothelial growth factor (VEGF) has mostly been tested to treat ischemic diseases, although the outcomes obtained are not satisfactory. Our hypothesis is that the local transient expression of VEGF and stem cell mobilizer granulocyte colony-stimulating factor (G-CSF) genes in ischemic limbs can complement their activities and be more efficient for limb recovery. Methods Limb ischemia was surgically induced in mice and 50 µg of VEGF and/or G-CSF genes were locally transferred by electroporation. After 3–4 weeks, evidence of necrosis by visual inspection, capillary density, muscle mass, muscle force and hematopoietic cell mobilization were evaluated. Results After 4 weeks, 70% and 90% of the animals of the ischemic group (IG) and VEGF-treated group (VG), respectively, presented limb necrosis, in contrast to only 10% observed in the group of mice treated with both VEGF and G-CSF genes (VGG). Recovery of muscle mass and muscle force was higher than 60% in the VGG compared to the non-ischemic group. The mobilization of Sca1+ cells and neutrophils was also higher in the VGG, which may explain the lower level of necrosis observed in this group (22%, in contrast to 70% in the IG). Capillary density and degree of fibrosis were determined in weeks 3 and 4, and also showed a clear benefit as a result of the use of the G-CSF and VEGF genes together. Conclusions Gene therapy using VEGF and G-CSF demonstrated a synergistic effect promoting vessel and tissue repair in mouse hind limb ischemia. Copyright © 2010 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text