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Am J Physiol Heart Circ Physiol (March 25, 2004). doi:10.1152/ajpheart.01141.2003
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Submitted on December 1, 2003
Accepted on March 22, 2004

Bone Marrow Stromal Cells Improve Cardiac Performance in Healed Infarcted Rat Hearts

Emerson Lopes Olivares1, Vanessa P. Ribeiro1, Joao Pedro S.W. de Castro1, Karla C. Ribeiro1, Elisabete C. De Mattos2, Regina C.S. Goldenberg1, Jose G. Mill3, Hans F. Dohmann4, Ricardo R. Dos Santos5, Antonio C. Campos de Carvalho6*, and Masako Oya Masuda1

1 Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
2 Ecodata Exames Medicos LTDA, Vitoria, Rio de Janairo, Brazil
3 Department of Ciencias Fisiologicas da UFES, Vitoria-ES, Brazil
4 Hospital Pro-Cardiaco, Rio de Janeiro, Rio de Janeiro, Brazil
5 Fundacao Oswaldo Cruz, Centro de Pesquisa Goncalo Muniz, Salvador, BA, Brazil
6 Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil; Department of Neuroscience, Albert Eisntein College of Medicine, New York, New York, USA

* To whom correspondence should be addressed. E-mail: acarlos{at}biof.ufrj.br.

Post-infarct congestive heart failure is one of the leading causes of morbidity and mortality in developed and developing countries. The main purpose of this study was to investigate whether transplantation of bone marrow stromal cells (BMSC) directly into the myocardium could improve the performance of healed infarcted rat hearts. Cell culture medium with or without BMSC was injected in the borders of cardiac scar tissue four weeks after the experimental infarction. Cardiac performance was evaluated two weeks after cellular (n = 10) or medium (n = 10) injection through electro and echocardiography. Histological study was performed three weeks after treatment. Compared to mediumtreated, the ECG of the BMSC-treated infarcted rats showed electrical and mechanical parameters more similar to those found in control animals: a normal frontal QRS axis in 6 out of 10 rats, while in the medium-treated group it was deviated to the right in all 10 animals. BMSC-treatment, assessed by echocardiographic parameters, improved fractional shortening (39.00 ± 4.03%) when compared to medium-treated hearts (18.20 ± 0.74%) and prevented additional changes in cardiac geometry. Immunofluorescence microscopy revealed co-localization of DAPI labeled nuclei of transplanted cells with cytoskeletal markers for cardiomyocytes and smooth muscle cells, indicating regeneration of the damaged myocardium and angiogenesis. These data provide strong evidence that BMSC implant can improve cardiac performance in healed infarctions and open new promising therapeutic opportunities for patients with post-infarction heart failure.




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