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

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dc.contributor.authorSacramento, Chester Bittencourt
dc.contributor.authorSilva, Flavia Helena da
dc.contributor.authorNardi, Nance Beyer
dc.contributor.authorYasumura, Eduardo Gallatti
dc.contributor.authorCosta Baptista-Silva, Jose Carlos [UNIFESP]
dc.contributor.authorBeutel, Abram [UNIFESP]
dc.contributor.authorCampos, Ruy Ribeiro de [UNIFESP]
dc.contributor.authorMoraes, Jane Zveiter de [UNIFESP]
dc.contributor.authorSilva Junior, Hamilton
dc.contributor.authorSamoto, Vivian Yochiko
dc.contributor.authorBorojevic, Radovan
dc.contributor.authorHan, Sang Won [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed Rio Grande do Sul
dc.contributor.institutionExcell Biomed Serv
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionDIPRO Inst Nacl Metrol Normalizacao & Controle Qu
dc.date.accessioned2016-01-24T13:59:23Z
dc.date.available2016-01-24T13:59:23Z
dc.date.issued2010-03-01
dc.description.abstractBackground 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.en
dc.description.affiliationUniversidade Federal de São Paulo, CINTERGEN UNIFESP, Interdisciplinary Ctr Gene Therapy, BR-04044010 São Paulo, Brazil
dc.description.affiliationUniv Fed Rio Grande do Sul, Dept Genet, BR-90046900 Porto Alegre, RS, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Surg, BR-04044010 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Physiol, BR-04044010 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, BR-04044010 São Paulo, Brazil
dc.description.affiliationExcell Biomed Serv, Rio de Janeiro, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Biomed, BR-21941 Rio de Janeiro, Brazil
dc.description.affiliationDIPRO Inst Nacl Metrol Normalizacao & Controle Qu, Rio de Janeiro, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, CINTERGEN UNIFESP, Interdisciplinary Ctr Gene Therapy, BR-04044010 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Surg, BR-04044010 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Physiol, BR-04044010 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, BR-04044010 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 0659630-0
dc.format.extent310-319
dc.identifierhttp://dx.doi.org/10.1002/jgm.1434
dc.identifier.citationJournal of Gene Medicine. Chichester: John Wiley & Sons Ltd, v. 12, n. 3, p. 310-319, 2010.
dc.identifier.doi10.1002/jgm.1434
dc.identifier.issn1099-498X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32312
dc.identifier.wosWOS:000275733700008
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofJournal of Gene Medicine
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectangiogenesisen
dc.subjectelectroporationen
dc.subjectGCSFen
dc.subjectlimb ischemiaen
dc.subjectVEGFen
dc.titleSynergistic effect of vascular endothelial growth factor and granulocyte colony-stimulating factor double gene therapy in mouse limb ischemiaen
dc.typeinfo:eu-repo/semantics/article
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