Cardiac Surgery Resident University of Alberta Edmonton, Alberta, Canada
Background: Tissue-engineered heart valves (TEHV) recellularized with allogenic mesenchymal stem cells (MSC) have shown promise in mitigating the immune rejection associated with structural valve deterioration. While the immunomodulatory benefits of MSC-seeded TEHV have been demonstrated, the hemodynamic performance has not been tested under acute physiologic pressures in a large animal setting. This study aimed to evaluate whether xenogenic ovine pulmonary valves recellularized with allogenic porcine MSCs maintain their acute hemodynamic function following pulmonary valve replacement in a porcine model.
METHODS AND RESULTS: Methods Sixteen pigs underwent pulmonary valve replacement using one of four valve types: untreated native ovine pulmonary valve, decellularized ovine valve, recellularized ovine valve with allogenic porcine MSCs, or sham control with donor porcine valve. Ovine pulmonary valves were decellularized with detergent-based washing and recellularized with approximately 25 million adipose-derived porcine MSCs. Pulmonary valve replacements were performed via median sternotomy under cardiopulmonary bypass. At 4 hours post-implantation, transthoracic echocardiography assessed peak jet velocity, pressure gradient, pulmonary regurgitation, left and right ventricular fractional area change (FAC), leaflet mobility, and calcification. Gross explants were photographed to evaluate leaflet integrity and thrombus formation.
Results There were no statistically significant adverse acute valvular hemodynamic changes following MSC recellularization (Figure 1). Peak pulmonary valve jet velocities (p = 0.35) and pressure gradients (p = 0.43) remained within normal limits across all groups, with no evidence of pulmonary stenosis. Although decellularized valves exhibited a higher degree of pulmonary regurgitation, this difference did not reach statistical significance (p = 0.13). All other groups demonstrated less than mild insufficiency. Biventricular function, as assessed by left and right ventricular FAC, remained within normal ranges (p = 0.55 and p = 0.73, respectively). Leaflet mobility was preserved, and gross explant examination showed intact structural architecture with no evidence of thrombosis or macroscopic degeneration.
Conclusion: Xenogenic pulmonary valves recellularized with allogenic MSCs preserved acute hemodynamic function following pulmonary valve replacement in a porcine model. These findings support the mechanical feasibility of MSC-based TEHVs under physiological conditions and establish a foundation for future long-term durability studies. Recellularized TEHVs may offer a scalable, immune-compatible, and non-thrombogenic alternative for biologic valve replacement.
