Bone marrow stromal cells improve cardiac performance in healed infarcted rat hearts

• Published in: American journal of physiology. Heart and circulatory physiology 2004-08, Vol.287 (2), p.H464-H470
• Main Authors: Olivares, Emerson Lopes, Ribeiro, Vanessa P, Werneck de Castro, Joao P. S, Ribeiro, Karla C, Mattos, Elisabete C, Goldenberg, Regina C. S, Mill, Jose G, Dohmann, Hans F, dos Santos, Ricardo Ribeiro, de Carvalho, Antonio C. Campos, Masuda, Masako Oya
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - analysis; Bone Marrow Transplantation; Echocardiography; Electrocardiography; Heart - physiopathology; Immunohistochemistry; Male; Myocardial Infarction - diagnosis; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Myocardial Infarction - surgery; Rats; Rats, Wistar; Wound Healing
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01141.2003

1 Instituto de Biofísica Carlos Chagas Filho UFRJ, Rio de Janeiro RJ, CEP-21949-900; 2 Ecodata Exames Médicos LTDA, Rio de Janeiro RJ, CEP-22020-120; 3 Departamento de Ciências Fisiológicas da UFES, Vitória ES, CEP-29040-090; 4 Hospital Pró-Cardíaco, Rio de Janeiro RJ, CEP-22251-150; and 5 Centro de Pesquisa Gonçalo Muniz, Fundação Oswaldo Cruz, Salvador BA, CEP-40295-00, Brazil; and 6 Albert Einstein College of Medicine, Bronx, New York 10461 Submitted 1 December 2003 ; accepted in final form 22 March 2004 Postinfarct 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 into borders of cardiac scar tissue 4 wk after experimental infarction. Cardiac performance was evaluated 2 wk after cellular ( n = 10) or medium ( n = 10) injection by electro- and echocardiography. Histological study was performed 3 wk after treatment. Electrocardiography of BMSC-treated infarcted rats showed electrical and mechanical parameters more similar to those in control than in medium-treated animals: a normal frontal QRS axis in 6 of 10 BMSC-treated and all control rats and a rightward deviation of the QRS axis in all 10 medium-treated animals. BMSC treatment, assessed by echocardiography, improved fractional shortening (39.00 ± 4.03%) compared with medium-treated hearts (18.20 ± 0.74%) and prevented additional changes in cardiac geometry. Immunofluorescence microscopy revealed colocalization of 4',6-diamidino-2-phenylindole-labeled nuclei of transplanted cells with cytoskeletal markers for cardiomyocytes and smooth muscle cells, indicating regeneration of damaged myocardium and angiogenesis. These data provide strong evidence that BMSC implantation can improve cardiac performance in healed infarctions and open new promising therapeutic opportunities for patients with postinfarction heart failure. myocardial infarction; cell therapy Address for reprint requests and other correspondence: A. C. Campos de Carvalho, Instituto de Biofísica Carlos Chagas Filho, UFRJ CCS, Bloco G, Ilha do Fundão, 21949-900 Rio de Janeiro RJ, Brazil (E-mail: acarlos{at}biof.ufrj.br ).