Combined endothelial cell-cardiac myocyte transplantation synergistically promoted ischemic myocardial repair and improved cardiac function in an acute myocardial infarction mouse model.
Combined endothelial cell and cardiac myocyte transplantation promotes ischemic myocardial repair via β1-integrin signaling in a preclinical AMI model.
BACKGROUND: In normal hearts, capillaries are densely distributed throughout the myocardial tissue, and the cross-talk between myocytes and capillary endothelial cells plays a pivotal role in regulating cardiac development, maturation and function. Although previous studies have suggested a role for the endothelium in the organisation of nearby cardiomyocytes, the underlying mechanism has yet to be illustrated. METHODS AND RESULTS: Using a transwell coculture system, we studied the paracrine effect of endothelial cells on cardiomyocytes and found that the regulation of cardiomyocyte spatial reorganisation and cytoskeletal dynamics by endothelial cells was coupled with β1-integrin induction. To determine the role of β1-integrin in this process, we preincubated myocytes with a β1-integrin function-blocking antibody before coculture. β1-integrin blockage abolished myocyte chemotactic activity and inhibited microtubule extension and stress fibre assembly. We further evaluated the therapeutic potential of combined endothelial cell-cardiac myocyte transplantation against ischemic cardiomyopathy in an acute myocardial infarction (AMI) mouse model. The results showed that myocytes and endothelial cells synergistically promoted ischemic myocardial repair, as evidenced by the robust engraftment and migration of implanted cells within the infarcted area, as well as the stimulation of angiogenesis, the attenuation of scar tissue and the improvement of cardiac function. CONCLUSION: Our study demonstrated the necessity of β1-integrin in the interactions between cardiomyocytes and endothelial cells and presented a novel combined transplantation approach that might hold promise for treating ischemic cardiomyopathy.
Zhang et al. (2015) studied Ischemic cardiomyopathy / Acute myocardial infarction. Combined endothelial cell-cardiac myocyte transplantation was evaluated on Ischemic myocardial repair, angiogenesis, scar tissue attenuation, and cardiac function. Combined endothelial cell-cardiac myocyte transplantation synergistically promoted ischemic myocardial repair and improved cardiac function in an acute myocardial infarction mouse model.