AUTHOR=Fallon John , Sagar Alex , Elzawahry Mohamed , Sadik Hatem , Gyoten Kazuyuki , Abbas Syed Hussain , Dumbill Richard , Friend Peter TITLE=The Hitchhiker's guide to isolated organ perfusion: a journey to 2040 JOURNAL=Frontiers in Transplantation VOLUME=Volume 4 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/transplantation/articles/10.3389/frtra.2025.1642724 DOI=10.3389/frtra.2025.1642724 ISSN=2813-2440 ABSTRACT=Building on the established success of hypothermic machine perfusion (HMP) and emerging normothermic platforms, machine perfusion is poised to guide a journey toward 2040, transforming organ transplantation into an era of integrated preservation, viability assessment, and ex situ therapy. While renal HMP today reduces delayed graft function and improves graft survival, the next two decades will centre on adaptive platform trials in normothermic perfusion, predictive AI-driven biomarkers, and unified registries to validate robust surrogate endpoints. Centralised Assessment and Reconditioning Centres (ARCs) will streamline 24/7 workflows, combining advanced imaging, molecular assays, and gene or cell therapies to repair and optimise grafts ex-vivo. Health economics will shift toward dynamic, value-based reimbursement, addressing equity and cost-effectiveness across diverse systems. Regulatory frameworks will adapt through CONSORT-style reporting and direct device-to-registry data integration, ensuring transparency and reproducibility. By 2040, these convergent advances in HMP, normothermic machine perfusion (NMP), along with translational research will not only enhance graft utilisation and patient outcomes but will redefine transplantation paradigms through precision graft management, optimised logistics, and new indications such as extracorporeal organ support.