Novel, Innovative Models to Study Ischemia/Reperfusion-Related Redox Damage in Organ Transplantation

Abstract

The implementation of ex vivo organ machine perfusion (MP) into clinical routine undoubtedly helped to increase the donor pool. It enables not just organ assessment, but potentially regeneration and treatment of marginal organs in the future. During organ procurement, redox-stress triggered ischemia-reperfusion injury (IRI) is inevitable, which in addition to pre-existing damage negatively affects such organs. Ex vivo MP enables to study IRI-associated tissue damage and its underlying mechanisms in a near to physiological setting. However, research using whole organs is limited and associated with high costs. Here, in vitro models well suited for early stage research or for studying particular disease mechanisms come into play. While cell lines convince with simplicity, they do not exert all organ-specific functions. Tissue slice cultures retain the three-dimensional anatomical architecture and cells remain within their naïve tissue-matrix configuration. Organoids may provide an even closer modelling of physiologic organ function and spatial orientation. In this review, we discuss the role of oxidative stress during ex vivo MP and the suitability of currently available in vitro models to further study the underlying mechanisms and to pretest potential treatment strategies.