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

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

Autor Goncalves, G. A. Google Scholar
Vassallo, P. F. Google Scholar
Santos, L. dos Google Scholar
Schettert, I. T. Google Scholar
Nakamuta, J. S. Google Scholar
Becker, C. Google Scholar
Tucci, Paulo José Ferreira Autor UNIFESP Google Scholar
Krieger, J. E. Google Scholar
Instituição Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
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
Assunto gene cell therapy
VEGF
angiogenic growth factors
cardiac repair
angiogenesis gene therapy
biopolymer scaffold
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Ministerio da Ciencia e Tecnologia
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Ministerio da Saude/Departamento Ciencia e Tecnologia
Número do financiamento FAPESP: 01/00090
Ministerio da Saude/Departamento Ciencia e Tecnologia: 552324/20005-1
Ministerio da Saude/Departamento Ciencia e Tecnologia: 10120104096700
FAPESP: 04/06784-4
FAPESP: 03/02671-8
FAPESP: 03/02672-4
Data 2010-03-01
Publicado em Gene Therapy. London: Nature Publishing Group, v. 17, n. 3, p. 305-314, 2010.
ISSN 0969-7128 (Sherpa/Romeo, fator de impacto)
Editor Nature Publishing Group
Extensão 305-314
Fonte http://dx.doi.org/10.1038/gt.2009.146
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000275392600002
URI http://repositorio.unifesp.br/handle/11600/32290

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