Cardiac xenotransplantation: a promising way to treat advanced heart failure


Cardiac xenotransplantation (CXTx) might be a promising approach to bridge the gap between the supply and demand of a donor heart. The survival of cardiac xenograft has been significantly extended in pig-to-nonhuman primate (NHP) CXTx, with records of 195 days and 945 days for orthotropic and heterotopic CXTx, respectively. To present the history of CXTx, we list the reported clinical CXTx, compare pigs and NHPs as sources of hearts, and compare three different kinds of preclinical CXTx models. The application of genetically modified pigs and novel immunosuppressive drugs accelerates the development of CXTx, and we summarize the reported pig-to-NHP CXTx with detailed information. Besides, we discuss the underlining mechanisms and potential preventive strategies of immunological barriers, including hyperacute rejection, acute humoral xenograft rejection, acute cellular xenograft rejection, chronic rejection, coagulation dysfunction, and systemic inflammation. Though intense cellular infiltration in cardiac xenograft has only been documented in a small number of studies, we especially stress the importance of cellular rejection in CXTx, because we believe it is often masked by the rapid and strong humoral response and it may eventually become a more important and common type of xenograft rejection. In addition, we conclude other obstacles as well as possible solutions in CXTx, such as perioperative cardiac xenograft dysfunction, detrimental xenograft overgrowth, and porcine endogenous retroviruses. Finally, we briefly introduce several other approaches that have been proposed to deal with the organ heart shortage crisis, and we firmly believe that CXTx provides the best near-term solution.

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Fig. 1
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Anti-CD154 monoclonal antibody


Anti-CD20 monoclonal antibody


Anti-CD40 monoclonal antibody


Activated protein C


Acute cellular xenograft rejection


Antibody-dependent cytotoxicity


Acute humoral xenograft rejection


Antigen-presenting cell




β-1,4-N-Acetyl-galactosa-minyl transferase 2


Consumptive coagulation


Cyclophosphamide, cyclosporine A, and steroids/corticosteroids


Cytidine monophosphate-N-acetylneuraminic acid hydroxylase


Complement receptor type 1


C-reactive protein


Cobra venom factor


Cardiac xenotransplantation


Delayed xenograft rejection


Fc receptor


Food and Drug Administration


Glycoprotein 1b




Human complement regulatory proteins


Human endothelial protein C-receptor


Human thrombomodulin


Human tissue factor pathway inhibitor


Hyperacute rejection


Human leukocyte antigen class I


Immune globulin






International Society for Heart and Lung Transplantation


Membrane attack complex


Major histocompatibility antigens class I


Mycophenolate mofetil


Nonhuman primate


Natural killer


Protein C


Perioperative cardiac xenograft dysfunction


Programmed cell death 1


Programmed cell death ligand 1


Porcine endothelial cell


Porcine endogenous retrovirus


Signal regulatory protein α


Swine leukocyte antigen class I


Systemic inflammation in xenograft recipients


T cell receptors


Tissue factor


Transforming growth factor β


Thrombotic microangiopathy


Tumor necrosis factor-α


von Willebrand Factor


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Correspondence to Jiangping Song.

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Shu, S., Ren, J. & Song, J. Cardiac xenotransplantation: a promising way to treat advanced heart failure. Heart Fail Rev (2020).

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  • Cardiac xenotransplantation
  • Immunological barriers
  • Genetically engineered
  • Porcine endogenous retroviruses
  • Organ crisis