Enhanced recovery of disqualified donor organs using image-guided machine perfusion

描述(申请人提供)：仅在美国，每年就有76,000人死于肝病。移植是目前唯一公认的治疗方法，但有 是捐献器官的严重短缺。超过60%的候选人等待一年以上才能接受移植，大多数人病得太重，无法忍受这一手术。通过挽救不合格的捐赠器官来扩大现有的捐赠者池，这些数字可能会大大改善；保守估计，每年有6000个肝脏。我们和其他人已经通过实验证明，机器灌流是一种能够进行治疗并显著提高存活率的强大方法。机器灌流是一种为孤立的捐赠者器官提供人工身体和血液供应的方法。然而，与严格控制的实验肝脏不同，人类捐赠器官的特点是有很大程度的变异性，从一系列先前存在的共病到死亡的情况，以及在获取和运输过程中经历的热缺血和冷缺血的持续时间。目前还没有办法客观地评估单个器官的状况和恢复的可能性，这也阻碍了在机器灌流期间进行器官特异性治疗方案的开发。因此，机器灌流目前是盲目进行的，抑制了其真正的临床潜力和该领域的垂直进步。我们的长期目标是通过设计强有力的战略来提高基于整体器官和细胞的治疗的可用性，将器官短缺造成的死亡降至最低。拟议研究的目的是验证一种创新的成像方法，用于在采购时和灌流期间对捐赠器官进行定性和定量评估。这里描述的工作有望产生新的器官存活指标，使缺血的准确诊断和器官恢复的实时评估成为可能。这项工作的未来结果将是将其扩展到其他全身疾病状态，在灌流过程中指导实时的、特定于器官的干预，以及预测达到最佳恢复的时间。这些进展将促进机器灌流作为所有供体器官的动态保存系统的临床翻译。

DESCRIPTION (provided by applicant): In the United States alone, 76,000 lives are claimed by liver disease every year. Transplantation is currently the only established treatment, but there is a critical shortage of donor organs. More than 60% of candidates wait over a year to receive a transplant, the majority becoming too ill to tolerate the procedure. These numbers could be improved dramatically by expanding the available donor pool through the rescue of disqualified donor organs; conservatively estimated at 6,000 livers per year. We and others have shown experimentally that machine perfusion, an artificial body and blood supply for isolated donor organs, is a powerful methodology capable of administering treatment and significantly increasing viability. However, unlike tightly-controlled experimental livers, there is a large degre of variability that characterizes human donor organs, from a range of pre-existing comorbidities to the circumstances of death and the duration of warm and cold ischemia experienced during procurement and transportation. There is currently no way to objectively assess the status and therefore likelihood of recovery of individual organs, which also prevents the development of organ-specific treatment regimens to be administered during machine perfusion. Machine perfusion is therefore currently being conducted blindly, inhibiting its true clinical potential an vertical advancement of the field. Our long-term goal is to minimize deaths due to organ shortages by engineering robust strategies to enhance the availability of whole organ- and cell-based therapies. The objective of the proposed study is to validate an innovative imaging approach for qualitative and quantitative evaluation of donor organs at the time of procurement and during perfusion. The work described here is expected to produce novel metrics of organ viability enabling accurate diagnosis of ischemia and real-time evaluation of organ recovery. Future consequences of this work will be its expansion to other systemic disease states, guidance of real-time, organ- specific interventions during perfusion, and the prediction of time to optimal recovery. These developments will facilitate the clinical translation of machine perfusion as a dynamic preservation system for all donor organs.