Mesenchymal stem cells promote cardiomyocyte hypertrophy in vitro through hypoxia-induced paracrine mechanisms.

1. Mesenchymal stem cell (MSC) therapy for myocardial infarction has received increased attention since transplanted MSC were shown to improve cardiac function by transdifferentiating into cardiomyocytes and endothelial cells. However, recent studies have demonstrated that other mechanisms may contribute to the improvement in cardiac function observed after transplantation of MSC. The paracrine effect of MSC on cardiomyocyte is not clear. Thus, in the present study, we investigated the paracrine effect of MSC on the growth of neonatal rat cardiomyocytes in vitro. 2. Samples of MSC-conditioned medium (MSC-CM) were collected after rat MSC had been cultured under conditions of hypoxia and serum deprivation for 0, 3, 6, 9 or 24 h. Cardiomyocytes were then stimulated with the MSC-CM for 48 h. Then, the protein content, cell area, [(3)H]-leucine incorporation and atrial natriuretic factor-luciferase (ANF-Luc) expression of cardiomyocytes were measured. 3. The data showed that MSC-CM collected at different time points had different effects and that MSC-CM collected at 6 h significantly promoted cardiomyocyte hypertrophy by increasing total protein content, cell area, [(3)H]-leucine incorporation and ANF gene expression. 4. In conclusion, MSC-CM promoted cardiomyocyte hypertrophy in a paracrine manner. The results provide a better understanding of the mechanisms underlying the improvement in heart function after MSC transplantation.