Transplantation of fetal myocardial tissue into the infarcted myocardium of rat: A potential method for repair of infarcted myocardium?

Background: Unlike skeletal myocytes, mammalian adult cardiomyocytes cannot regenerate after injury. A possible strategy to increase viability and augment ventricular function after myocardial injury is fetal myocardial tissue transplantation. The engrafted fetal cells are a potential source of growth factors and can be used for cardiomyocyte-based gene therapy. The purpose of our study was to test the feasibility and efficiency of fetal cardiomyocyte transplantation into a model of myocardial infarction. Methods and Results: We subjected rats after myocardial infarction to three protocols of therapy. In the first protocol, tissue fragments of cultures human fetal ventricles were injected into the scar 7 to 24 days after infarction. The rats were treated with intraperitoneal injections of 12.5 mg · kg^-1 · d^{- 1} cyclosporine. In the second protocol, fragments of cultured fetal rat ventricles were injected into the scar 9 to 7 days after infarction. A third group of animals with myocardial infarction was treated with injection of saline into the scar (control). After 7 to 65 days post-transplantation, hearts were harvested and processed for electron microscopy and α-actin immunohistochemistry. Toluidine blue staining and electron microscopy revealed the presence of engrafted human and rat cardiomyocytes in the infarcted myocardium up to 14 and 65 days after transplantation, respectively. The morphology was similar to that of cultured fetal cardiomyocytes. The engrafted fetal tissues were also stained positive for α-actin which is unusual for the adult rat myocardium. Examination of control hearts detected infarcted tissue only, and α-actin staining was limited to vessel walls. Conclusions: Fetal cardiomyocyte tissue can be implanted and survive in the infarcted myocardium. This experimental approach may provide a therapeutic strategy for cardiomyocyte-based gene therapy for introduction of therapeutic proteins into myocardial infarction.