The Experimental Study On Myocardial Infarction Therapy By Intracoronary Transplantation Of Lsogenic Bone Marrow Mononuclear Cells

Background and Objectives.Significant progress has been achieved during the past ten years in cell transplantation and recent research has focused on the possibility of improving ventricular function after myocardial infarction. Most studies in the field of cardiac tissue repair were performed by direct intramyocardial injection of cells of different origin. Since this approach requires a complicated surgical intervention, in this study we investigated the feasibility of intracoronary administration of isogenic bone marrow mononuclear cells (BMMNCs) by assessing the fate of transplanted , purified, labeled cells in ectopic transplanted cryodamaged hearts.Design and Methods.Donor and recipient inbred isogenic adult (8-10 weeks old) Lewis rats were used as models to mimic intracoronary transplantation of autologous bone marrow mononuclear cells in clinical setting. First, myocardial damage was obtained in the hearts of donor rats by placing a frozen metal rod on the anterior left ventricular wall for 20 seconds (freeze-thaw injury technique). Second, the injured hearts were procured and then isogenic heterotopic heart transplantation were performed in the cervical area of recipient rats. Third,Two days after the injury, isogenic BMMNCs were purified and labeled with PKH26 ( a red fluorescent cell dye) and approximate 2 l07 cells were infused through the coronary artery of infarcted transplanted hearts. Finally, seven days after the infusion, the infarcted and normal hearts, lungs, livers, kidneys, spleens and bone marrow were harvested from recipient rats to track the fate of transplanted, labeled BMMNCs.Results.Labeled cells were found only in the injured myocardium of treated animals and not in the normal tissue, and a limited number of cells were identified in the spleen and bone marrow of the treated recipients. Most of the labeled cells in the infarcted area were CD34 staining positive. Expression of connexin43 in the infarcted area of treated rats was significantly higher than in the infarcted area of controls.Conclusions.Our data suggest that intracoronarily injected BMMNCs can survive and traffic through the circulation to the site of damaged myocardium and may probably lead to regeneration of new myocardium. We hypothesize that tissue injury leads to the priming of a cytokine cascade acting as chemoattractant for the infused cells.