Abstract
Organ transplantation is undergoing profound changes. Contraindications for donation have been revised in order to better meet the organ demand. The use of lower-quality organs and organs with greater preoperative damage, including those from donation after cardiac death (DCD), has become an established routine but increases the risk of graft malfunction. This risk is further aggravated by ischemia and reperfusion injury (IRI) in the process of transplantation. These circumstances demand a preservation technology that ameliorates IRI and allows for assessment of viability and function prior to transplantation. Oxygenated hypothermic and normothermic machine perfusion (MP) have emerged as valid novel modalities for advanced organ preservation and conditioning. Ex vivo prolonged lung preservation has resulted in successful transplantation of high-risk donor lungs. Normothermic MP of hearts and livers has displayed safe (heart) and superior (liver) preservation in randomized controlled trials (RCT). Normothermic kidney preservation for 24 h was recently established. Early clinical outcomes beyond the market entry trials indicate bioenergetics reconditioning, improved preservation of structures subject to IRI, and significant prolongation of the preservation time. The monitoring of perfusion parameters, the biochemical investigation of preservation fluids, and the assessment of tissue viability and bioenergetics function now offer a comprehensive assessment of organ quality and function ex situ. Gene and protein expression profiling, investigation of passenger leukocytes, and advanced imaging may further enhance the understanding of the condition of an organ during MP. In addition, MP offers a platform for organ reconditioning and regeneration and hence catalyzes the clinical realization of tissue engineering. Organ modification may include immunological modification and the generation of chimeric organs. While these ideas are not conceptually new, MP now offers a platform for clinical realization. Defatting of steatotic livers, modulation of inflammation during preservation in lungs, vasodilatation of livers, and hepatitis C elimination have been successfully demonstrated in experimental and clinical trials. Targeted treatment of lesions and surgical treatment or graft modification have been attempted. In this review, we address the current state of MP and advanced organ monitoring and speculate about logical future steps and how this evolution of a novel technology can result in a medial revolution.
Highlights
The velocity and significance of progress in transplantation started to decrease around the turn of the century
Patient survival as an endpoint followed by graft survival as a surrogate and indicator of judicious organ attribution were the framework of significant momentum that succeeded in making transplantation a standard of care
Static cold storage (SCS) has been successfully applied over decades with good outcomes in standard criteria donor (SCD) organs, at present, marginal or expanded criteria donor (ECD) organs in particular are increasingly preserved by hypothermic (HMP) or normothermic machine perfusion (NMP) technologies
Summary
The velocity and significance of progress in transplantation started to decrease around the turn of the century. Patient survival as an endpoint followed by graft survival as a surrogate and indicator of judicious organ attribution were the framework of significant momentum that succeeded in making transplantation a standard of care. With the pressure to maintain and further improve the excellent short- and long-term results, but working with very different resources, the most prominent immediate challenge is to better define and preserve, if not improve, organ quality in transplantation. With this as a driving force, modalities to prolong and improve preservation together with the tools to assess organ quality and function are emerging as the new frontier. The assessment of the outcome after transplantation of extended criteria organs, needs to be seen and interpreted with reference to the diverse definitions used throughout the years
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