Westhaver Lauren P, Nersesian Sarah, Arseneau Riley J, Hefler Joshua, Hargreaves Breanna K V, Edgar Alexander, Azizieh Yara, Cuesta-Gomez Nerea, Izquierdo Dayne L, Shapiro A M James, Gala-Lopez Boris L, Boudreau Jeanette E
Department of Pathology, Dalhousie University, Halifax, NS, Canada.
Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
Heliyon. 2024 Feb 24;10(5):e27122. doi: 10.1016/j.heliyon.2024.e27122. eCollection 2024 Mar 15.
normothermic machine perfusion (NMP) preserves donor organs and permits real-time assessment of allograft health, but the most effective indicators of graft viability are uncertain. Mitochondrial DNA (mtDNA), released consequent to traumatic cell injury and death, including the ischemia-reperfusion injury inherent in transplantation, may meet the need for a biomarker in this context. We describe a real time PCR-based approach to assess cell-free mtDNA during NMP as a universal biomarker of allograft quality. Measured in the perfusate fluid of 29 livers, the quantity of mtDNA correlated with metrics of donor liver health including International Normalized Ratio (INR), lactate, and warm ischemia time, and inversely correlated with inferior vena cava (IVC) flow during perfusion. Our findings endorse mtDNA as a simple and rapidly measured feature that can inform donor liver health, opening the possibility to better assess livers acquired from extended criteria donors to improve organ supply.
常温机器灌注(NMP)可保存供体器官并允许对同种异体移植物的健康状况进行实时评估,但移植物活力的最有效指标尚不确定。创伤性细胞损伤和死亡(包括移植中固有的缺血再灌注损伤)导致线粒体DNA(mtDNA)释放,在这种情况下,mtDNA可能满足对生物标志物的需求。我们描述了一种基于实时PCR的方法,用于评估NMP期间无细胞mtDNA,作为同种异体移植物质量的通用生物标志物。在29个肝脏的灌注液中测量发现,mtDNA的数量与供体肝脏健康指标相关,包括国际标准化比值(INR)、乳酸和热缺血时间,并且与灌注期间下腔静脉(IVC)流量呈负相关。我们的研究结果支持将mtDNA作为一种简单且可快速测量的特征,它能够反映供体肝脏的健康状况,为更好地评估从扩大标准供体获取的肝脏以改善器官供应开辟了可能性。