Repair of Myocardial Infarction by Epicardial Deposition of Bone Marrow Cell-Coated Muscle Patch in a Murine Model

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 × 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 β-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 × 10 6 β-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 β-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.