Cell therapy using human cardiac progenitors cell-seeded collagen patches applied on failing overloaded right ventricle: A new step toward the treatment of right heart failure?

Right ventricular (RV) failure is a major concern in grown-up congenital heart diseases. Cell-based myocardial repair may be an innovative approach to restore overloaded RV function. A repaired Tetralogy of Fallot pig model was used. After 5 months, cell therapy was surgically administrated using human embryonic stem cell-derived Nkx2.5+ cardiac progenitor cell-seeded collagen patch. A large patch containing 107 cells was engineered to cover the whole RV free wall and applied on the epicardium of 4 pigs (treated group). A control group (n = 4) received a cell-free patch (3) or no patch (1). Myocardial function was assessed by echocardiography using standard and strain parameters before and 2 months after cell graft. The fate of progenitors was tracked using human-and cardiac specific antibodies. Indexed RV diameter and telediastolic RV area significantly decreased in treated group whereas increased in control. The free wall thickness significantly increased in treated group compared to control. In the treated group, RV free wall strain significantly improved by contrast to control (respectively from −13.4 to −15.9% vs. −18.9 to −12.9%, P  Fig. 1 ). Although still immature, some cells featured TnT+ actinin+ sarcomeric units. Proliferating small Ki-67+ TnT+ labelled pig myocytes were observed. Expression of collagen genes col1a3, col3a1 monitored in real-Time QPCR reflecting myocardial fibrosis status significantly decreased in the treated group. Human cardiac progenitors migrated and differentiated, contributing together with triggered endogenous mechanism of repair to maintain the RV adaptation to overload and to improve free wall contractility. They also induced a proliferation of host cells supporting potential paracrine effects.