ORIGINAL RESEARCH article

Front. Cardiovasc. Med.

Sec. Heart Failure and Transplantation

Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1549377

This article is part of the Research TopicEmerging Techniques in Graft Preservation: Machine Perfusion and Therapeutic Interventions - Volume IIView all 3 articles

Porcine Model of Acute Rejection for Cardiac Transplantation

Provisionally accepted
Michelle Mendiola PlaMichelle Mendiola Pla1Yuting ChiangYuting Chiang2Carolyn GlassCarolyn Glass1David C WendellDavid C Wendell1Devjanee Swain LenzDevjanee Swain Lenz1Sam HoSam Ho3Marat FudimMarat Fudim1Franklin H LeeFranklin H Lee1Lillian KangLillian Kang1Matthew F SmithMatthew F Smith1Alejandro Alvarez LoboAlejandro Alvarez Lobo1Kishen MitraKishen Mitra1Ryan T GrossRyan T Gross1Chunbo WangChunbo Wang1Muath BishawiMuath Bishawi4Andrew VeksteinAndrew Vekstein1Krish DewanKrish Dewan1Jeng-Wei ChenJeng-Wei Chen5Amy EvansAmy Evans1Kristianne M OristianKristianne M Oristian1Salvatore PizzoSalvatore Pizzo1Jie LiJie Li1Laura HaleLaura Hale1Paul M LezbergPaul M Lezberg6Carmelo A MilanoCarmelo A Milano1Dawn BowlesDawn Bowles1*
  • 1Duke University Medical Center, Duke University, Durham, North Carolina, United States
  • 2Aurora St. Luke's Medical Center, Milwaukee, Wisconsin, United States
  • 3Gift of Hope, Itasca, Illinois, United States
  • 4School of Medicine, Emory University, Atlanta, Georgia, United States
  • 5National Taiwan University Hospital, Taipei, Taiwan
  • 6TransMedics, Inc., Andover, Maine, United States

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Ex vivo machine perfusion has been growing in utility for preserving donor organs prior to transplantation. This modality has tremendous potential for bioengineering and conditioning organs prior to transplantation using small molecule or advanced therapeutics. To safely translate potential interventions, well characterized models of disease are crucial for testing the therapeutic and possible side effects that could manifest from the interventions. Acute cellular rejection remains a significant complication in organ transplantation that affects transplant recipients with significant morbidity and mortality. This disease could potentially be mitigated with therapeutic intervention during ex vivo machine perfusion. A porcine animal model of acute rejection could be characterized in order to translate human biological processes with high fidelity. The Yucatan pig breed has been increasingly used in both biomedical research and xenotransplantation applications given its similarity to the human heart. A challenge with utilizing this pig breed for designing a model of acute rejection is its highly conserved ancestral lineage, which could make it difficult to induce acute rejection in a timely and consistent manner. We present a detailed characterization of a porcine model of acute rejection based on swine leukocyte antigen mismatching paired with a limited period of clinically relevant immunosuppression. The result is a robust and consistent protocol that results in fulminant acute rejection of an intra-abdominally transplanted heart.

Keywords: acute rejection, Cardiac transplantation, Machine perfusion, disease model, Translational research

Received: 21 Dec 2024; Accepted: 12 May 2025.

Copyright: © 2025 Mendiola Pla, Chiang, Glass, Wendell, Swain Lenz, Ho, Fudim, Lee, Kang, Smith, Lobo, Mitra, Gross, Wang, Bishawi, Vekstein, Dewan, Chen, Evans, Oristian, Pizzo, Li, Hale, Lezberg, Milano and Bowles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dawn Bowles, Duke University Medical Center, Duke University, Durham, 27710, North Carolina, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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