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Static cold storage (SCS) offers a simple and effective way to preserve and transport organs and is the most commonly used method4. However, a number of limitations are associated with SCS, including tissue damage induced by prolonged hypothermic preservation, difficulty in assessing donor organ function and viability, inevitability of ischemia-reperfusion injury (IRI), and limited opportunity for organ repair. Recently, the growing use of marginal organs from extended criteria donors has led to an emergence of ex vivo lung perfusion (EVLP) to assess donor lung function5,6. In addition to being an excellent graft assessment tool, EVLP has also shown potential for enabling graft repair, reconditioning, and immunomodulation7, which inspired similar research and clinical applications in other organ systems8,9,10. The desire to extend preservation times has motivated research on optimal preservation solutions, temperatures, techniques, and therapeutic additives for organ repair and reconditioning11,12,13,14. By reviewing the history of organ perfusion and preservation, we noted that before the introduction of SCS in 1960s15, machine perfusion with plasma or blood-based solutions was the clinical method for preserving isolated organs16,17. Reevaluating the advantages and limitations of early organ perfusion/preservation may help with the development of new techniques/solutions that enable prolonged safe preservation and the repair of extended criteria donor organs to address the organ shortage issue. Theories, preservation techniques, preservation solutions, and clinical practices are discussed.
To avoid the use of human blood products, interest has increased in acellular oxygen carriers, which have similar oxygen carrying capacity to human hemoglobin111. Initial studies on hemoglobin-based oxygen carriers have shown encouraging results, including enhanced oxygenation and improved allograft function of ex vivo perfused organs in normothermic/subnormothermic conditions106,112, which opens the door for blood substitution in future.
In liver, studies on therapeutic medications during NMP to reduce IRI showed promising results in pigs and rats133,134,135. Goldaracena et al delivered an antiviral drug to perfusate during normothermic ex vivo liver perfusion and effectively induced Hepatitis C virus resistance after pig liver transplantation136. 2b1af7f3a8