Intravenous infusion of cardiac progenitor cells in animal models of single ventricular physiology.

Abstract

The goal of this study was to identify the practical applications of intravenous cell therapy for single-ventricle physiology (SVP) by establishing experimental SVP models. An SVP with a three-stage palliation was constructed in an acute swine model without cardiopulmonary bypass. A modified Blalock-Taussig (MBT) shunt was created using an aortopulmonary shunt with the superior and inferior venae cavae (SVC and IVC, respectively) connected to the left atrium (n = 10). A bidirectional cavopulmonary shunt (BCPS) was constructed using a graft between the IVC and the left atrium with an SVC cavopulmonary connection (n = 10). The SVC and the IVC were connected to the pulmonary artery to establish a total cavopulmonary connection (TCPC, n = 10). The survival times of half of the animal models were studied. The other half and the biventricular sham control (n = 5) were injected intravenously with cardiosphere-derived cells (CDCs), and the cardiac retention of CDCs was assessed after 2 h. All SVP models died within 20 h. Perioperative mortality was higher in the BCPS group because of lower oxygen saturation (P < 0.001). Cardiac retention of intravenously delivered CDCs, as detected by magnetic resonance imaging and histologic analysis, was significantly higher in the modified Blalock-Taussig and BCPS groups than in the TCPC group (P < 0.01). Without the total right heart exclusion, stage-specific SVP models can be functionally constructed in pigs with stable outcomes. Intravenous CDC injections may be applicable in patients with SVP before TCPC completion, given that the initial lung trafficking is efficiently bypassed and sufficient systemic blood flow is supplied from the single ventricle.