Effects of allogenic bone marrow mesenchymal stem cell transplantation on electrophysiological abnormality and left ventricular remodeling in rats with myocardial infarction / 中国组织工程研究

ABSTRACT

BACKGROUND: Stem cell transplantation in repairing infarct myocardium and in improving cardiac function has been widely accepted. However, whether transplanted cells and host cells formed an effective electricity and mechanical couple, whether a relevant independent electrical system with contractile function formed or whether severe malignant ventricular arrhythmia formed, are still unclear.OBJECTIVE: To investigate electrophysiological abnormaltiy and left ventricular remodeling in rats with myocardial infarction following allogenic bone marrow mesenchymal stem cell (BMSC) transplantation.DESIGN, TIME AND SETTING: The randomized controlled animal study was performed at the Experimental Center, Guangxi Medical University from December 2005 to October 2008.MATERIALS: A total of 120 healthy Wistar rats were equally randomized into normal control, sham operation, saline control and cell transplantation groups. Healthy Wister rats aged 1 month were selected to harvest bone marrow.METHODS: At the third passage, rat BMSCs were collected and treated with 5-aza, and differentiated into cerdiomyocytes.BMSCs were labeled with DAPI at 2 hours before transplantation. In the saline control and cell transplantation groups, rat models of myocardial infarction were established by ligating the left anterior descending coronary artery. In the sham operation group, the coronary artery was not ligated, but only braid. At 7 days following ligation, BMSCs in the cell transplantation group at 2×10-1/L were infused into the edge and center of myocardial infarct region by multipoint injection. Rats in the other three groups were subjected to an equal volume of saline.MAIN OUTCOME MEASURES: Electrocardiogram and cardiac electrophysiology were performed. Ultrasonic cardiography was used to detect left ventricular function. Infarct size was determined. DAPl-labeled donor cell migration and distribution was observed with a fluorescence microscope.RESULTS: BMSCs could differentiate into cardiacmuscle cell-like cells which were capable of pulsing spontaneously, expressing cardiactoponin T and forming myofilament in vitro. Compared with the saline control group, PR interval, QRS duration and ventdcular effective refractory period shortened, ventricular fibrillation threshold increased at 4, 8 and 12 weeks (P < 0.05); left ventricular internal diameter at end-systole reduced, and left ventricular ejection fraction and shortening traction was significantly increased (P< 0.05). At 8 and 12 weeks, infarct size was significantly smaller (P < 0.05). At 4 weeks, DAPl-labeled BMSCs could be seen under the fluorescence microscope, and still could he detected at 12 weeks. However, the fluorescence became weak with prolonged time.CONCLUSION: BMSCs have the plasticity of differentiating into cardiac muscle cell-like cells, which can modulate theelectrophysiological abnormality and left ventricular remodeling following myocardial infarction.