Abstract
Ex-situ machine perfusion (MP) techniques are increasingly used in clinical settings, especially on grafts derived from donors after cardiac death (DCD). However, comprehension of biological effects elicited during MP are largely unknown and a substantial number of animal studies are presently focused on this topic. The aim of the present study was to describe a model of DCD based on ex-situ perfusion of liver grafts derived from animals dedicated to food production. Procurement took place within a slaughterhouse facility. A clinically fashioned closed circuit normothermic MP (NMP) was built up. Autologous blood-enriched perfusion fluid was adopted. Perfusate and tissue samples were collected to asses NMP functionality. Grafts were classified as transplantable (LT-G) or not (n-LT) according to clinical criteria, while histopathological analysis was used to confirm graft viability. After cold storage, the liver grafts were connected to the NMP. During the rewarming phase, temperature and flows were progressively increased to reach target values. At the end of NMP, 4 grafts were classified as LT-G and 3 nLT-G. Histology confirmed absence of major damage in LT-G, while diffuse necrosis appeared in nLT-G. Interestingly, in nLT-G an early impairment of hepatocyte respiratory chain, leading to cell necrosis and graft non-viability, was documented for the first time. These parameters, together with indocyanine-green dye and citrate clearance could contribute to graft evaluation in clinical settings. In conclusion, this model provides a promising and reproducible method to replace dedicated experimental animals in DCD and MP research, in line with the 3Rs principles.
Highlights
Over the last few years, the increased number of patients requiring organ transplantation has caused a challenging organ shortage as the number of suitable donors has remained relatively stable
The present research shows that organs retrieved from a slaughterhouse can be used as a model of liver donors after cardiac death (DCD) donation
DCD donors are considered a valuable potential resource to increase the number of organs suitable for transplantation (Manyalich et al, 2018)
Summary
Over the last few years, the increased number of patients requiring organ transplantation has caused a challenging organ shortage as the number of suitable donors has remained relatively stable. In 2017, according to the annual report of the Scientific Registry of Transplant Recipients (SRTR), 1334 patients died on the waiting list for a liver in the USA, while 703 liver grafts were not transplanted (Kim et al, 2019). To overcome this shortage, liver grafts from high risk donors ( called extended criteria donors, ECD) are increasingly used such grafts generally show a poorer outcome after liver transplantation (LT) (Vodkin and Kuo, 2017). The DCD-related problems mainly stem from prolonged warm ischemia time (WIT), which reduces the tissue energy pool leading to cell death (Merlen et al., ALTEX 37(2), 2020
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