AUTHOR=Mendiola Pla Michelle , Chiang Yuting , Glass Carolyn , Wendell David C. , Swain-Lenz Devjanee , Ho Sam , Fudim Marat , Lee Franklin H. , Kang Lillian , Smith Matthew F. , Alvarez Lobo Alejandro , Mitra Kishen , Gross Ryan T. , Wang Chunbo , Bishawi Muath , Vekstein Andrew , Dewan Krish , Chen JengWei , Evans Amy , Roki Antonio , Ferrell Paul , Oristian Kristianne M. , Pizzo Salvatore V. , Li Jie , Hale Laura P. , Lezberg Paul M. , Milano Carmelo A. , Bowles Dawn E. 

TITLE=A porcine model of acute rejection for cardiac transplantation

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1549377

DOI=10.3389/fcvm.2025.1549377

ISSN=2297-055X

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.