Synergistic effect of vascular endothelial growth factor and granulocyte colony-stimulating factor double gene therapy in mouse limb ischemia

Synergistic effect of vascular endothelial growth factor and granulocyte colony-stimulating factor double gene therapy in mouse limb ischemia

Author Sacramento, Chester Bittencourt Google Scholar
Silva, Flavia Helena da Google Scholar
Nardi, Nance Beyer Google Scholar
Yasumura, Eduardo Gallatti Google Scholar
Costa Baptista-Silva, Jose Carlos Autor UNIFESP Google Scholar
Beutel, Abram Autor UNIFESP Google Scholar
Campos, Ruy Ribeiro de Autor UNIFESP Google Scholar
Moraes, Jane Zveiter de Autor UNIFESP Google Scholar
Silva Junior, Hamilton Google Scholar
Samoto, Vivian Yochiko Google Scholar
Borojevic, Radovan Google Scholar
Han, Sang Won Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande do Sul
Excell Biomed Serv
Universidade Federal do Rio de Janeiro (UFRJ)
DIPRO Inst Nacl Metrol Normalizacao & Controle Qu
Abstract 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 mu g 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 (C) 2010 John Wiley & Sons, Ltd.
Keywords angiogenesis
limb ischemia
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 0659630-0
Date 2010-03-01
Published in Journal of Gene Medicine. Chichester: John Wiley & Sons Ltd, v. 12, n. 3, p. 310-319, 2010.
ISSN 1099-498X (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 310-319
Access rights Closed access
Type Article
Web of Science ID WOS:000275733700008

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