Mitochondrial DNA levels in perfusate and bile during ex vivo normothermic machine correspond with donor liver quality

Lauren P Westhaver; Sarah Nersesian; Riley J Arseneau; Joshua Hefler; Breanna K V Hargreaves; Alexander Edgar; Yara Azizieh; Nerea Cuesta-Gomez; Dayne L Izquierdo; A M James Shapiro; Boris L Gala-Lopez; Jeanette E Boudreau

doi:10.1016/j.heliyon.2024.e27122

Mitochondrial DNA levels in perfusate and bile during ex vivo normothermic machine correspond with donor liver quality

Heliyon. 2024 Feb 24;10(5):e27122. doi: 10.1016/j.heliyon.2024.e27122. eCollection 2024 Mar 15.

Authors

Lauren P Westhaver¹, Sarah Nersesian^{2

3}, Riley J Arseneau¹, Joshua Hefler⁴, Breanna K V Hargreaves⁵, Alexander Edgar², Yara Azizieh¹, Nerea Cuesta-Gomez^{4

6}, Dayne L Izquierdo⁴, A M James Shapiro^{4

6}, Boris L Gala-Lopez^{1

2

3

7}, Jeanette E Boudreau^{1

2

3}

Affiliations

¹ Department of Pathology, Dalhousie University, Halifax, NS, Canada.
² Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
³ Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada.
⁴ Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada.
⁵ Dalhousie Medical School NS, Dalhousie University, Halifax, NS, Canada.
⁶ Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.
⁷ Department of Surgery, Dalhousie University, Halifax, NS, Canada.

Abstract

Ex vivo 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.

Keywords: Extended criteria organ donation; Liver transplantation; Mitochondrial DAMPs; Mitochondrial DNA; Normothermic organ perfusion; Organ health assessment; Solid organ transplantation.