Clinical Evolution, Outcomes, and Emerging Preservation Technologies in Pancreas and Islet Transplantation

Historically regarded as competitive modalities, pancreas and islet transplantation are increasingly recognized as complementary approaches to beta-cell replacement therapy. While whole-organ pancreas transplantation remains the established gold standard, islet transplantation has transitioned into an effective clinical alternative for selected cohorts of patients suffering from type 1 diabetes. This review provides a comprehensive evaluation of the clinical evolution characterizing these therapeutic modalities, tracing the shift from static cold storage (SCS) toward innovative dynamic preservation technologies, and exploring potential markers for predicting clinical outcomes. A focus on immunosuppression in islet transplantation is provided, emphasizing precise, tolerance-inducing strategies and investigating costimulation blockade, regulatory T-cell (Treg)-based therapies, and biomaterial-enabled local immunoprotection, with the aim of facilitating long-term graft survival while mitigating the metabolic and renal toxicities secondary to chronic calcineurin inhibitor exposure. Current evidence related to the transition from conventional SCS to advanced perfusion platforms, namely hypothermic machine perfusion (HMP), oxygenated hypothermic perfusion (HOPE), normothermic ex vivo perfusion (NEVP), and normothermic regional perfusion (NRP) is examined: the literature suggests that dynamic pancreas preservation platforms may improve metabolic recovery and some islet isolation outcomes; however, evidence that HOPE specifically reduces ischemia-reperfusion injury and consistently increases islet yield in the pancreas remains limited. Although normothermic perfusion provides significant utility for real-time viability assessment and graft reconditioning, its widespread clinical implementation remains constrained by technical impediments, notably interstitial edema. Ultimately, preservation efficacy is conceptualized not merely as a discrete preservation option, but as a multidimensional construct integrating biological integrity, graft usability, and recipient clinical outcomes.