Abeline R. Watkins, B.Sc: No financial relationships to disclose
Nicholas M. Fialka, MD: No financial relationships to disclose
Background: Valvular heart disease (VHD) is an increasing problem in healthcare today with its end stage requiring surgical intervention. The current valve replacement options available today, however, still have considerable limitations to their use. Mechanical valves require patients to adhere to lifelong anti-coagulation while bioprosthetic valves undergo structural valvular deterioration requiring subsequent re-operations. Tissue-engineering has been proposed as a method to create another valve replacement option that reduces the immune-related effects of bioprosthetic valves without requiring anticoagulation. By decellularizing full-sized harvested porcine aortic valves and recellularizing them with cultured human mesenchymal progenitor cells (hMPC), we expect to create an attenuated immune response compared to decellularized bioprosthetic tissue alone.
METHODS AND RESULTS: Six tissue-engineered full-sized aortic valves were created by decellularizing porcine aortic valves (PAV) and recellularizing them with cultured human hMPCs. A recellularized (rPAV), decellularized (dPAV), native (nPAV), and human pericardium (HP) sample were each exposed to human whole blood, and blood plasma samples were analyzed for cytokine concentrations on exposure days 1, 3, and 5 using ELISA. rPAV had significantly less pro-inflammatory cytokine (TNFa, INFy, IL1b, and IL-12 p40) expression on exposure days 1 and 5 compared to decellularized tissue alone, with similar or less expression of pro-inflammatory cytokines INFy, IL-6, and GM-CSF compared to human pericardium control samples (P < 0.05).
Conclusion: Recellularizing bioprosthetic tissue provides an immune advantage over decellularization alone suggesting that tissue-engineered heart values could attenuate the immune-regulated degradation of current bioprosthetic valves. Recellularized valves also are shown to be similar in cytokine expression to human tissue controls, demonstrating no increased inflammatory risk of this process. These results are promising that recellularized valves could be a potential new option to valve replacement in the future by increasing their durability without requiring anticoagulation.
