A porcine model of acute rejection for cardiac transplantation

Michelle Mendiola Pla, Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC, United States.
Yuting Chiang, Advocate Health - MidwestFollow
Carolyn Glass, Department of Pathology, Duke University Medical Center, Durham, NC, United States.
David C. Wendell, Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Durham, NC, United States.
Devjanee Swain-Lenz, Sequencing and Genomics Technologies Core Facility, Duke University School of Medicine, Durham, NC, United States.
Sam Ho, Gift of Hope Organ and Tissue Donor Network, Itasca, IL, United States.
Marat Fudim, Department of Cardiology, Duke University Medical Center, Durham, NC, United States.
Franklin H. Lee, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.
Lillian Kang, Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC, United States.
Matthew F. Smith, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.
Alejandro Alvarez Lobo, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.
Kishen Mitra, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.
Ryan T. Gross, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.
Chunbo Wang, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.
Muath Bishawi, Division of Cardiothoracic Surgery, Emory University Medical Center, Atlanta, GA, United States.
Andrew Vekstein, Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC, United States.
Krish Dewan, Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC, United States.
JengWei Chen, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Amy Evans, Perfusion Services, Duke University Medical Center, Durham, NC, United States.
Antonio Roki, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.
Paul Ferrell, Department of Pathology, Duke University Medical Center, Durham, NC, United States.
Kristianne M. Oristian, Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States.
Salvatore V. Pizzo, Department of Pathology, Duke University Medical Center, Durham, NC, United States.
Jie Li, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.
Laura P. Hale, Department of Pathology, Duke University Medical Center, Durham, NC, United States.
Paul M. Lezberg, TransMedics, Inc., Andover, MA, United States.
Carmelo A. Milano, Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC, United States.
Dawn E. Bowles, Division of Surgical Science, Duke University Medical Center, Durham, NC, United States.

Affiliations

Aurora St. Luke's Medical Center

Abstract

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.

Document Type

Article

PubMed ID

40756599

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