Background. Myocardial infarction results in irreversible myocyte loss. In a murine model, we tested the feasibility of a novel repair technique combining bone marrow cell (BMC) transplantation and cardiomyoplasty. Methods. Myocardial infarction was induced cryogenically in backcrossed ROSA 26 transgenic X C57BL/6J mice (n = 75). Thirty days later, surviving mice (n = 69) were randomized to sham treatment (rethoracotomy only; n = 11), patch only treatment (n = 29), or patch + BMC treatment (n = 29). Abdominal muscle patches were harvested from donor littermates not expressing the beta-galactosidase reporter gene and sutured on the epicardium directly above the infarct zone. Patch only-treated mice received uncoated patches. Patch + BMC-treated mice received patches coated with 5 X 10(6) beta-galactosidase-expressing BMCs embedded in a collagen-rich three-dimensional matrix. Results. Mortality rate was 52% after muscle patch implantation. Bone marrow cells were able to migrate from muscle patch into the infarct zone, as demonstrated by P-galactosidase immunostaining, and ultimately constituted 8% of all cells in scar tissue (mean +/- standard deviation, 219 +/- 111/mm(2)). Angiogenesis and cell survival in the scar were improved by patch + BMC treatment. Left ventricular geometry and cardiac function were improved by patch treatment, with or without BMC, although the effects were stronger after patch + BMC treatment. Conclusions. Epicardial deposition of a BMC-coated muscle patch is a promising approach to restoring cardiac function after myocardial infarction. (C) 2004 by The Society of Thoracic Surgeons.
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Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, CanadaUniv Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, Canada
Al-Radi, OO
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Rao, V
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Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, CanadaUniv Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, Canada
Rao, V
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Li, RK
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Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, CanadaUniv Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, Canada
Li, RK
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Yau, T
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Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, CanadaUniv Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, Canada
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Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, CanadaUniv Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, Canada
Al-Radi, OO
;
Rao, V
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Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, CanadaUniv Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, Canada
Rao, V
;
Li, RK
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Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, CanadaUniv Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, Canada
Li, RK
;
Yau, T
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Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, CanadaUniv Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiac Surg, Toronto, ON M5G 1L7, Canada