Intramyocardial transplantation of fibroblasts expressing vascular endothelial growth factor attenuates cardiac dysfunction

Autor(es)

Goncalves, G. A. ; Vassallo, P. F. ; dos Santos, L. ; Schettert, I. T. ; Nakamuta, J. S. ; Becker, C. ; Tucci, P. J. F. ^[1] ; Krieger, J. E. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Cardiac Physiol & Physiopathol Lab, Dept Physiol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Lab Genet & Mol Cardiol, Heart Inst InCor, Dept Med, BR-05403000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Gene Therapy; v. 17, n. 3, p. 305-314, MAR 2010.
• Citações Web of Science: 15

Resumo

In this study, we analyzed whether transplantation of cardiac fibroblasts (CFs) expressing vascular endothelial growth factor (VEGF) mitigates cardiac dysfunction after myocardial infarction (MI) in rats. First, we observed that the transgene expression lasts longer (45 vs 7 days) when fibroblasts are used as vectors compared with myoblasts. In a preventive protocol, induction of cardiac neovascularization accompanied by reduction in myocardial scar area was observed when cell transplantation was performed 1 week before ischemia/reperfusion and the animals analyzed 3 weeks later. Finally, the therapeutic efficacy of this approach was tested injecting cells in a fibrin biopolymer, to increase cardiac retention, 24 h post-MI. After 4 weeks, an increase in neovascularization and a decrease in myocardial collagen were observed only in rats that received cells expressing VEGF. Basal indirect or direct hemodynamic measurements showed no differences among the groups whereas under pharmacological stress, only the group that received cells expressing VEGF showed a significant reduction in end-diastolic pressure and improvement in stroke volume and cardiac work. These results indicate that transplantation of CFs expressing VEGF using fibrin biopolymer induces neovascularization and attenuates left ventricle fibrosis and cardiac dysfunction in ischemic heart. Gene Therapy (2010) 17, 305-314; doi:10.1038/gt.2009.146; published online 10 December 2009 (AU)

• Processo FAPESP: 04/06784-4 - Capacidade de transdiferenciação das células mesenquimais do tecido adiposo: estudo no reparo cardiovascular
• Beneficiário: Juliana Sanajotti Nakamuta
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 03/02671-8 - Modelo de terapia gênica associada à terapia celular no estudo da progressão e extensão do infarto do miocárdio
• Beneficiário: Claudia Becker
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 03/02672-4 - Terapia celular com miofibroblastos cardíacos modificados geneticamente para produzir VEGF e/ou IGF-1 para prevenção de lesão pós-injúria cardíaca
• Beneficiário: Giovana Aparecida Gonçalves
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto