Effects of auto-skeletal muscle satellite cell transplantation on myocardial fibrosis in myocardial infarction rats / 中国组织工程研究

ABSTRACT

BACKGROUND:Myocardial fibrosis following myocardial infarction is an important mechanism of ventricle reconstitution. However, there are few reports concerning effects of myocardial transplantation related to stern cells on this process. OBJECTIVE: To investigate the effects of auto-skeletal muscle satellite cells implanted into ischemic myocardium on myocardial fibrosis in rats with myocardial infarction and their mechanisms.DESIGN, TIME AND SETTING: The randomized controlled animal study was performed at the Third Research Room, Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA from July to September 2007. MATERIALS A total of 45 Wistar rats, of both genders, weighing 150-200 g, were used in this study. Of them, 30 rats were used to establish models of myocardial infarction.METHODS: A total of 45 rats were assigned to 3 groups (n=15). Rats in the myocardial infarction group received ligation of the left anterior descending coronary artery to induce myocardial infarction. 2 weeks later, 0.2 mL serum-free M199 medium was infused into the juncture between infarct region and normal myocardium through multiple points. In the transplantation group, following model induction, 0.2 mL auto-skeletal muscle satellite cells in rats after 2-weeks in vitro culture were transplanted into the surrounding of infarct region. Rats in the sham operation group were not induced to create models, only injected with 0.2 mL saline in the heart anterior wall surrounding the left anterior descending branch through multiple points. MAIN OUTCOME MEASURES: Four weeks after injection, vascular endothelial growth factor mRNA and vascular endothelial growth factor protein expression in the ischemic myocardium was demonstrated. Capillary density changes in the ischemic myocardium were detected. Growth and proliferation of myocardial cells in the infarct region were observed using hematoxylin-eosin staining.RESULTS: Vascular endothelial growth factor mRNA and vascular endothelial growth factor protein expression was significantly decreased in the sham operation and myocardial infarction groups compared with the transplantation group at 4 weeks following satellite cell transplantation (P<0.01). Capillary density was greater in the myocardial infarction group compared with the sham operation group (P<0.05). Capillary density was significantly higher in the rat ischemic myocardium in the transplantation group compared with the sham operation and myocardial infarction groups (P<0.01). Hematoxylin-eosin staining demonstrated that myocardial morphology was normal in rats of the sham operation group, with clear structure, orderly myocardial fibrosis. There were no fibroblastaggregation and hyperplasia among myocardial fibrosis. Fibroblast hyperplasia and collagent formation were found in the rat myocardium in the myocardial infarction group, with disorderly myocardial structure. Myocardial cells with transverse striation and many nuclei were observed in the rat infarct region of the transplantation group, with orderly arrangement. Fibrous tissue was significantly less in the transplantation group compared with the myocardial infarction group.CONCLUSION: Satellite cells can proliferate and differentiate into striated muscle-like cells with flexible and systolic functions in the infarct region. Satellite cells secrete vascular endothelial growth factor and promote blood capillary hyperplasia in ischemic myocardium by autocrine and paracrine, which finally effectively inhibits fibrosis progress in the ischomic myocardium.