Progenitor Cell Heart Therapy The capacity of the differentiated CPCs to form mechanical inter-connections with neonatal rat ventricular cardiomyocytes was assessed in vitro (Figs. 5e, f). Isolated GFP(+) CPCs were co-cultured with NRVMs and subsequently assayed for GFP and N-Cadherin expression which mediates adhesion in the intercalated discs at the termini of cardiomyocytes thereby serving as a mechanical anchor for myofibrils at cell-cell contacts [20]. The GFP(+) cardiomyocytes, which were readily distinguishable from the NRVMs, formed N- Cadherin(+) intercalated disc cell contracts with the NRVMs. Determination of cardiac functional output by echocardiographic evaluation Myocardial infarction injury produced a time-dependent ventricular dilatation and left ventricular dysfunction (Fig. 6). Over a 4-week time span the control group (saline-injected infracted animals), exhibited a 50% increase (2.8060.2 mm to 4.260.2 mm) of the left ventricular internal diastolic diameter (LVIDd, Fig. 6a) and an 84% increase (1.6360.2 mm to 3.060.3 mm) of the left ventricular internal systolic diameter Figure 6. Echocardiographic analysis. Time course of structural and hemodynamic indices obtained using echocardiography in the four studied groups. The left ventricular size in diastole (a) and systole (b) increased in the saline injected infarct control group while in CPC treated and sham groups it remained stable over 4 weeks after MI injury (p,0.01). Similarly, the ejection fraction (c) and fractional shortening (d) decreased in the saline infracted control group while in CPC treated groups remained stable over 4 weeks post infraction (p,0.01). Note that over the course of treatment neither of 4 indices differed between CPC treated infracted heart and sham groups injected with saline or CPC. doi:10.1371/journal.pone.0011536.g006 PLoS ONE | www.plosone.org 8 July 2010 | Volume 5 | Issue 7 | e11536