Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view

Abstract

Ex vivo machine perfusion (EVMP) is an emerging technique for preserving explanted solid organs with primary application in allogeneic organ transplantation. EVMP has been established as an alternative to the standard of care static-cold preservation, allowing for prolonged preservation and real-time monitoring of organ quality while reducing/preventing ischemia–reperfusion injury. Moreover, it has paved the way to involve expanded criteria donors, e.g., after circulatory death, thus expanding the donor organ pool. Ongoing improvements in EVMP protocols, especially expanding the duration of preservation, paved the way for its broader application, in particular for reconditioning and modification of diseased organs and tumor and infection therapies and regenerative approaches. Moreover, implementing EVMP for in vivo-like preclinical studies improving disease modeling raises significant interest, while providing an ideal interface for bioengineering and genetic manipulation. These approaches can be applied not only in an allogeneic and xenogeneic transplant setting but also in an autologous setting, where patients can be on temporary organ support while the diseased organs are treated ex vivo, followed by reimplantation of the cured organ. This review provides a comprehensive overview of the differences and similarities in abdominal (kidney and liver) and thoracic (lung and heart) EVMP, focusing on the organ-specific components and preservation techniques, specifically on the composition of perfusion solutions and their supplements and perfusion temperatures and flow conditions. Novel treatment opportunities beyond organ transplantation and limitations of abdominal and thoracic EVMP are delineated to identify complementary interdisciplinary approaches for the application and development of this technique.

Novel portable hypothermic machine perfusion preservation device enhances cardiac viability of donated human hearts

“…This study aimed to evaluate the feasibility of the VP.S ENCORE® device to preserve human donor-derived hearts not utilized for transplant for prolonged time. Study results revealed that hypothermic machine perfusion (HMP) between 4 and 10°C contributes to the reduction of the active metabolic state in cardiac grafts, as measured by low lactate and other myocardial markers expression, thereby minimizing the risk of the accumulation of toxic metabolites while maintaining cardiac viability ( 26 ). Examination of various metabolic markers, including oxygen consumption and lactate levels, demonstrated notable correlations with myocardial function during machine perfusion ( 4 ).…”

Editorial: Immunosenescence in organ transplantation

“…For their application in transplantation, the most efficacious deployment of senolytics needs to be evaluated. Hereby, treatment of the donor, the recipient, and the organ itself by recruiting ex vivo perfusion systems ( 24 , 25 ) need to be compared to ensure most efficient treatment while sparing side effects.…”

Tissue Injury Protection: The Other Face of Anticoagulant Treatments in the Context of Ischemia and Reperfusion Injury with a Focus on Transplantation

“…Studies are still ongoing to determine and/or improve the optimal perfusion solution and its gaseous composition, system temperature, flow conditions, etc. Currently, perfusate contains several pharmacologic components to maintain vascular homeostasis and is heparinized to avoid thrombosis of the system [43].…”