Normothermic Regional Perfusion in Pancreas and Islet Transplantation From Donation After Circulatory Death Donors: A Comprehensive Overview

ABSTRACT: Several strategies have been used to mitigate ischemic injury and optimize graft quality in pancreas and islet transplantation, particularly in the context of donation after circulatory death (DCD) donors. These include conventional rapid recovery with static cold storage, optimized DCD retrieval protocols designed to reduce warm ischemia and, more recently, the use of machine perfusion techniques. Normothermic regional perfusion (NRP) represents a distinct approach within this landscape, enabling the restoration of oxygenated blood flow in situ, partial metabolic recovery, and the potential for functional evaluation before organ retrieval. Available clinical experience with NRP in DCD pancreas and islet transplantation indicates that the technique is feasible and safe, with graft and islet isolation results comparable with those achieved with conventional DCD procurement strategies. Nevertheless, overall experience remains limited and important aspects of NRP frameworks require further refinement. This review provides a comprehensive synthesis of the current evidence on DCD beta-cell replacement, with a particular focus on NRP as an emerging strategy to mitigate ischemic injury. We summarize available clinical and registry-based data, discuss the physiological rationale supporting NRP, and outline key gaps in donor selection, perfusion protocols, and outcome assessment. Finally, we identify priorities for future research aimed at optimizing NRP practice and expanding the pancreas donor pool while improving posttransplant graft and patient outcomes.