Beyond the icebox: modern strategies in organ preservation for transplantation

Abstract

Organ transplantation, a critical treatment for end-stage organ failure, has witnessed significant advancements due to the integration of improved surgical techniques, immunosuppressive therapies, and donor-recipient matching. This review explores the progress of organ preservation, focusing on the shift from static cold storage (SCS) to advanced machine perfusion techniques such as hypothermic (HMP) and normothermic machine perfusion (NMP). Although SCS has been the standard approach, its limitations in preserving marginal organs and preventing ischemia-reperfusion injury (IRI) have led to the adoption of HMP and NMP. HMP, which is now the gold standard for high-risk donor kidneys, reduces metabolic activity and improves posttransplant outcomes. NMP allows real-time organ viability assessment and reconditioning, especially for liver transplants. Controlled oxygenated rewarming further minimizes IRI by addressing mitochondrial dysfunction. The review also highlights the potential of cryopreservation for long-term organ storage, despite challenges with ice formation. These advances are crucial for expanding the donor pool, improving transplant success rates, and addressing organ shortages. Continued innovation is necessary to meet the growing demands of transplantation and save more lives.

Keywords: Cryopreservation; Machine perfusion; Nanobiotechnology; Organ transplantation.

Fig. 1

Progression of temperature trends in organ machine perfusion. Hypothermic machine perfusion (HMP): blue-shaded, hypothermic oxygenated perfusion (HOPE): gray-shaded, subnormothermic machine perfusion (SNMP): yellow-shaded, normothermic machine perfusion (NMP): green shaded, controlled oxygenated rewarming (COR): orange-shaded [–62].

Fig. 2

Pictures of organ perfusion platforms: hypothermic, normothermic, and our lab’s innovations. (A) OrganOx Metra System: normothermic machine perfusion currently in clinical trials (with permission of OrganOx), (B) LifePort Liver Transporter: hypothermic machine perfusion currently in clinical trials (with permission of Organ Recovery Systems), and (C) BioCool Organ Preservation Machine: Hanyang’s Regenerative Medicine and Stem Cells institution hypothermic machine perfusion.

Fig. 3

Schematic illustration of ice formation and cryoinjury. EC, extracellular; conc, concentration; IC, intracellular.

Fig. 4

Diagrammatic illustration of the role of cryoprotective agents (CPAs) in subzero preservation: permeable CPAs (pCPAs) and nonpermeable CPAs (npCPAs). EC, extracellular; IC, intracellular.

Fig. 5

Classification of cryopreservation techniques by temperature and principle of ice preservation.