Progress in Orthotopic Pig Heart Transplantation in Nonhuman Primates
Review
doi: 10.3389/ti.2024.13607.
eCollection 2024.
Affiliations
Item in Clipboard
Review
Transpl Int.
.
Abstract
Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6-9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial.
Keywords:
costimulation blockade; genetically-modified pig; organ perfusion; orthotopic heart transplantation; xenotransplantation.
Copyright © 2024 Längin, Bender, Schmoeckel and Reichart.
Conflict of interest statement
ML and BR are founding members of XTransplant GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
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Waterworth PD, Dunning J, Tolan M, Cozzi E, Langford G, Chavez G, et al. Life-supporting Pig-To-Baboon Heart Xenotransplantation. J Heart Lung Transpl (1998) 17:1201–7.
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PubMed
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MeSH terms
Grants and funding
The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. Financial support was provided by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) TRR 127.
Fonte original PubMed