Abstract 1076: Forced Expression of Myocardin in Mesenchymal Stem Cells from Ischemic Heart Disease Patients Induces Differentiation Into a Cardiomyocyte Phenotype and Improves Left Ventricular Function after Myocardial Infarction in NOD/scid Mice
Background: Little is known about the differentiation capability of human mesenchymal stem cells (hMSCs) obtained from patients with ischemic heart disease (IHD). We investigated if forced expression of the cardiac transcription factor Myocardin (Myoc) induces hMSCs to acquire a cardiomyocyte phenotype in vivo, and improves left ventricular (LV) function in a mouse myocardial infarction (MI) model.
Methods: hMSCs from IHD patients were transfected either with eGFP + Myoc (hMSCmyoc) or eGFP alone (hMSCGFP). After MI induction, hMSCmyoc (n=10), hMSCGFP (n=10) or vehicle only (control, n=11) were injected into the infarct area of immune-compromised NOD/scid mice. Sham operated mice were used as baseline. After 2 and 14 days, LV volumes and ejection fraction (EF) were serially assessed using an animal 9.4T MRI. After 14 days immunostaining was performed.
Results: At day 2 no differences in LV volumes and EF were found between the groups (Fig⇓.). At day 14 there was a higher EF in both hMSC groups as compared to the control group (P<0.02). Furthermore, hMSCmyoc but not hMSCGFP reduced ESV and EDV as compared to the control group (P=0.01 and P=0.03 respectively). hMSCs engrafted in the infarcted area. In the hMSCmyoc group, hMSCs expressed the cardiomyocyte markers cardiac troponin I (cTnI) and Atrial Natriuretic Factor (ANF). In contrast, this was not observed in the hMSCGFP group.
Conclusions: Transplantation of hMSCmyoc further decreases LV remodelling compared to hMSCGFP alone. Furthermore, forced expression of Myoc induced differentiation into a cardiomyocyte phenotype. These data suggest that hMSCmyoc may constitute an improved form of hMSC therapy for the treatment of IHD.