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
Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC, United States.
Division of Cardiovascular and Thoracic Surgery, Aurora St. Luke's Medical Center, Milwaukee, WI, United States.
Front Cardiovasc Med. 2025 Jul 18;12:1549377. doi: 10.3389/fcvm.2025.1549377. eCollection 2025.
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 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.
在器官移植前，机器灌注在保存供体器官方面的应用日益广泛。这种方式在利用小分子或先进疗法对器官进行生物工程改造和预处理方面具有巨大潜力。为了安全地转化潜在干预措施，特征明确的疾病模型对于测试干预措施可能产生的治疗效果和副作用至关重要。急性细胞排斥反应仍然是器官移植中的一个重大并发症，会给移植受者带来显著的发病率和死亡率。在机器灌注过程中进行治疗干预可能会减轻这种疾病。可以对急性排斥反应的猪动物模型进行特征描述，以便高度逼真地转化人类生物学过程。尤卡坦猪品种因其与人类心脏相似，在生物医学研究和异种移植应用中越来越多地被使用。利用这种猪品种设计急性排斥反应模型面临的一个挑战是其高度保守 的祖先谱系，这可能使其难以及时、一致地诱导急性排斥反应。我们基于猪白细胞抗原不匹配并结合有限期的临床相关免疫抑制，对急性排斥反应的猪模型进行了详细的特征描述。结果是一个强大且一致的方案，可导致腹腔内移植心脏的暴发性急性排斥反应。
