Experimental study on treatment of myocardial infarction by intracoronary transplantation of isogenic bone marrow mononuclear cells

Objective: To investigate the feasibility of intracoronary administration of isogenic bone marrow mononuclear cells（BMMNCs） by assessing the fate of transplanted,purified,labeled cells in ectopic transplanted cryo-damaged hearts in rats. Methods: Inbred isogenic adult（8-10 weeks old） Lewis rats were used as donors and recipients.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.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 2×10⁷ cells were infused through the coronary artery of infarcted transplanted hearts of the experimental group,while the control group were injected with DMEM.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: The myocardial degeneration and necrosis with clear border were identified in the cryo-injured heart of model rats by pathology.This model was successfully used to mimic intracoronary transplantation of autologous bone marrow mononuclear cells in clinical setting.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.Some 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 that in the infarcted area of controls. Conclusion: Our data suggest that intracoronarily injected BMMNCs can survive and traffic through the circulation to the site of damaged myocardium and may lead to regeneration of new myocardium.