Table 1_A porcine model of acute rejection for cardiac transplantation.docx

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.

离体机器灌注（ex vivo machine perfusion）在移植前供体器官保存领域的应用价值日益凸显。该技术在移植前借助小分子药物或先进治疗手段开展器官生物工程与预处理方面拥有巨大潜力。为安全地实现潜在干预手段的临床转化，需依托经过充分表征的疾病模型，以测试干预措施可能产生的治疗效果与潜在副作用。急性细胞排斥反应仍是器官移植领域的重大并发症，会显著提升移植受者的发病率与死亡率。此类疾病有望通过离体机器灌注期间的治疗干预得到缓解。为实现人类生物学过程的高保真复现，可构建并表征猪急性排斥反应动物模型。尤卡坦猪（Yucatan pig）因其与人类心脏的高度相似性，在生物医学研究与异种移植领域的应用愈发广泛。但利用该猪品种构建急性排斥反应模型面临一项核心挑战：其祖先谱系高度保守，这可能导致难以及时且稳定地诱导出急性排斥反应。本研究详细表征了一种基于猪白细胞抗原（swine leukocyte antigen, SLA）错配联合短期临床相关免疫抑制方案的猪急性排斥反应模型。该方案可形成稳定可靠的操作流程，能够诱导腹腔内移植心脏发生暴发性急性排斥反应。