0245: Cell therapy to restore overloaded right ventricular function: First promising results using human cardiac progenitors seeded in a patch on the epicardium

Background Despite the prevalence of right ventricular (RV) failure in congenital heart diseases, cell therapy applied to RV is poorly studied. Our aim is to evaluate in a large animal model of overloaded RV dysfunction such therapy using cardiac progenitors (CP) issued from human embryonic stem cells. Methods A combined overloaded RV dysfunction was created in pigs using a surgical procedure mimicking repaired tetralogy of Fallot. At 4 months, cell therapy was surgically administrated using either multiple transepicardial injections of HUES-24 derived CP into RV myocardium or CP seeded collagen patches sewn on RV free wall. SHAM animals received either multiple transepicardial injections of medium or acellular patches. Myocardial function was determined 3 months later by conductance catheter technique with maximal elastance (Emax) slope. Ventricular arrhythmia risks were tested by programmed ventricular stimulation. A histological study analyzed the structural remodelling. CP fate was studied using anti- Ki67, CD31, CD34, GFP, Islet1 and Connexin 43 antibodies. All pigs were immunosuppressed by Tacrolimus. Results All pigs survived. Neither complication nor ventricular arrhythmia occurred. In injected animals (SHAM: n=6, HUES-24: n=6) the Emax slope value evoluated similarly in both groups. Whereas total fibrosis increased significantly with time in the SHAM group, it returned to baseline in HUES-24 group. However, CP could not be found. In contrast, in patched animals, CP were found in the patch zone and close to the myocardium. These CP were able to proliferate, migrate, express cardiac markers and establish connexions. Conclusion Cell therapy using transepicardial injections of human CP seems to have a beneficial effect on overloaded RV tissue remodelling, but this administration mode did not improve myocardial contractility. Seeded patches seem to be more conservative for engrafted cells; their impact on overloaded RV function requires further experiments.