feedsFeeds PubMed

Progress in Orthotopic Pig Heart Transplantation in Nonhuman Primates


Review


doi: 10.3389/ti.2024.13607.


eCollection 2024.

Affiliations

Item in Clipboard

Review

Matthias Längin et al.


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.

PubMed Disclaimer

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.

Figures


FIGURE 1



FIGURE 1

Survival after orthotopic pig-to-baboon cardiac xenotransplantations from 1994 to 2023. Data taken from [, , –, –27].

References

    1. Fukushima N, Bouchart F, Gundry SR, Nehlsen-Cannarella S, Gusewitch G, Chang L, et al. The Role of Anti-pig Antibody in Pig-To-Baboon Cardiac Xenotransplant Rejection. Transplantation (1994) 57:923–8. 10.1097/00007890-199403270-00026



      DOI



      PubMed

    1. 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.



      PubMed

    1. Bhatti FN, Schmoeckel M, Zaidi A, Cozzi E, Chavez G, Goddard M, et al. Three-month Survival of HDAFF Transgenic Pig Hearts Transplanted into Primates. Transpl Proc (1999) 31:958. 10.1016/s0041-1345(98)01855-7



      DOI



      PubMed

    1. Lam TT, Hausen B, Squiers E, Cozzi E, Morris RE. Cyclophosphamide-Induced Postoperative Anemia in Cynomolgus Monkey Recipients of hDAF-Transgenic Pig Organ Xenografts. Transpl Proc (2002) 34:1451–2. 10.1016/s0041-1345(02)02925-1



      DOI



      PubMed

    1. Kuwaki K, Tseng Y-L, Dor FJMF, Shimizu A, Houser SL, Sanderson TM, et al. Heart Transplantation in Baboons Using Alpha1,3-Galactosyltransferase Gene-Knockout Pigs as Donors: Initial Experience. Nat Med (2005) 11:29–31. 10.1038/nm1171



      DOI



      PubMed

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

Artigos relacionados

Deixe um comentário

O seu endereço de e-mail não será publicado. Campos obrigatórios são marcados com *

Botão Voltar ao topo

Adblock detectado

Por favor, considere apoiar-nos, desativando o seu bloqueador de anúncios