Serial assessment of human adipose stem cell xenotransplantation in a rat myocardial infarction model

Human adipose stem cell (ASC) transplantation is of therapeutic potential in the treatment of myocardial infarction (MI). However, little is known with regard to the optimal time of cell transplantation for MI patients. This study was designed to discover the most beneficial time for cell transplantation with the goal of improving cardiac function. MI was induced in Sprague-Dawley (SD) rats by permanent ligation of the left anterior descending (LAD) coronary artery. ASCs (1×10⁶) were transplanted directly into the infarcted myocardium 1 -week (n=10), 2 -weeks (n=10), and 4 -weeks (n=10) post MI. At 2 and 4 weeks after cell transplantation, cardiac function was assessed by echocardiography. Four weeks after cell transplantation, immunohistochemical staining for fibronectin and troponin I, and Western blotting for VEGF, bax/bcl-2, and cleaved-caspase-9, were performed. Left ventricular function, especially ejection fraction (EF), showed a significant improvement in the 1- and 2-week groups compared to the PBS group 4 weeks after treatment (P< 0.05). However, there was no difference in the 4 -week group compared to the PBS group. There were more obvious decreases in the bax/bcl-2 ratio, expression of cleaved-caspase-9, and increased vascular density and expression of vascular endothelial growth factor (VEGF) in the 1-week group than the other groups (P<0.05). Based on the conditions studied, our results provide evidence that ASCs transplantation 1 week after MI exerted the best effect on the recovery of cardiac function in a rat MI model. Decreasing apoptosis and increasing neovascularization seem to contribute this effect partly.