RegenHeart: A Time-Effective, Low-Concentration, Detergent-Based Method Aiming for Conservative Decellularization of the Whole Heart Organ

Abstract

Heart failure is the worst outcome of all cardiovascular diseases and still represents nowadays the leading cause of mortality with no effective clinical treatments, apart from organ transplantation with allogeneic or artificial substitutes. Although applied as the gold standard, allogeneic heart transplantation cannot be considered a permanent clinical answer because of several drawbacks, as the side effects of administered immunosuppressive therapies. For the increasing number of heart failure patients, a biological cardiac substitute based on a decellularized organ and autologous cells might be the lifelong, biocompatible solution free from the need for immunosuppression regimen. A novel decellularization method is here proposed and tested on rat hearts in order to reduce the concentration and incubation time with cytotoxic detergents needed to render acellular these organs. By protease inhibition, antioxidation, and excitation-contraction uncoupling in simultaneous perfusion/submersion modality, a strongly limited exposure to detergents was sufficient to generate very well-preserved acellular hearts with unaltered extracellular matrix macro- A nd microarchitecture, as well as bioactivity.