Models of immunogenicity in preclinical assessment of tissue engineered heart valves

Tissue engineered heart valves may one day offer an exciting alternative to traditional valve prostheses. Methods of construction vary, from decellularised animal tissue to synthetic hydrogels, but the goal is the same: the creation of a 'living valve' populated with autologous cells that may persist indefinitely upon implantation. Previous failed attempts in humans have highlighted the difficulty in predicting how a novel heart valve will perform in vivo. A significant hurdle in bringing these prostheses to market is understanding the immune reaction in the short and long term. With respect to innate immunity, the chronic remodelling of a tissue engineered implant by macrophages remains poorly understood. Also unclear are the mechanisms behind unknown antigens and their effect on the adaptive immune system. No silver bullet exists, rather researchers must draw upon a number of in vitro and in vivo models to fully elucidate the effect a host will exert on the graft. This review details the methods by which the immunogenicity of tissue engineered heart valves may be investigated and reveals areas that would benefit from more research. STATEMENT OF SIGNIFICANCE: Both academic and private institutions around the world are committed to the creation of a valve prosthesis that will perform safely upon implantation. To date, however, no truly non-immunogenic valves have emerged. This review highlights the importance of preclinical immunogenicity assessment, and summarizes the available techniques used in vitro and in vivo to elucidate the immune response. To the authors knowledge, this is the first review that details the immune testing regimen specific to a TEHV candidate.