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.