CARDIOMYOCYTE TRANSPLANTATION IN A PORCINE MYOCARDIAL-INFARCTION MODEL

Transplantation of cardiomyocytes into the heart is a potential treatm ent for replacing damaged cardiac muscle. To investigate the feasibili ty and efficiency of this technique, either a cardiac-derived cell lin e (HL-1 cells), or normal fetal or neonatal pig cardiomyocytes were gr afted into a porcine model of myocardial infarction. The myocardial in farction was created by the placement of an embolization coil in the d istal portion of the left anterior descending artery in Yorkshire pigs (n = 9), Four to 5 wk after creation of an infarct, the three prepara tions of cardiomyocytes were grafted, at 1 x 10(6) cells/20 mu L into normal and into the middle of the infarcted myocardium. The hearts wer e harvested and processed for histologic examinations 4 to 5 wk after the cell grafts. Histologic evaluation of the graft sites demonstrated that HL-1 cells and fetal pig cardiomyocytes formed stable grafts wit hin the normal myocardium without any detrimental effect including arr hythmia, In addition, a marked increase in angiogenesis was observed b oth within the grafts and adjacent host myocardium. Electron microscop y studies demonstrated that fetal pig cardiomyocytes and the host myoc ardial cells were coupled with adherens-type junctions and gap junctio ns. Histologic examination of graft sites from infarct tissue failed t o show the presence of grafted HL-I cells, fetal, or neonatal pig card iomyocytes. Cardiomyocyte transplantation may provide the potential me ans for cell-mediated gene therapy for introduction of therapeutic mol ecules into the heart, (C) 1998 Elsevier Science Inc.