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 ca nnot regenerate after injury. A possible strategy to increase viabilit y and augment ventricular function after myocardial injury is fetal my ocardial tissue transplantation. The engrafted fetal cells are a poten tial 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 myo cardial infarction. Methods and Results We subjected rats after myocar dial infarction to three protocols of therapy. In the first protocol, tissue fragments of cultured human fetal ventricles were injected into the scar 7 to 24 days after infarction. The rats were treated with in traperitoneal injections of 12.5 mg . kg(-1).(-1) cyclosporine. In the second protocol, fragments of cultured fetal rat ventricles were inje cted into the scar 9 to 17 days after infarction. A third group of ani mals with myocardial infarction was treated with injection of saline i nto the scar (control). After 7 to 65 days post-transplantation, heart s were harvested and processed for electron microscopy and alpha-actin immunohistochemistry. Toluidine blue staining and electron microscopy revealed the presence of engrafted human and rat cardiomyocytes in th e infarcted myocardium up to 14 and 65 days after transplantation, res pectively. The morphology was similar to that of cultured fetal cardio myocytes. The engrafted fetal tissues were also stained positive for a lpha-actin, which is unusual for the adult rat myocardium. Examination of control hearts detected infarcted tissue only, and alpha-actin sta ining was limited to vessel walls. Conclusions Fetal cardiomyocyte tis sue can be implanted and survive in the infarcted myocardium. This exp erimental approach may provide a therapeutic strategy for cardiomyocyt e-based gene therapy for introduction of therapeutic proteins into myo cardial infarction.