Supercooling: a promising technique for prolonged preservation in solid organ transplantation, and early perspectives in vascularized composite allografts

Abstract

Ex vivo preservation of transplanted organs is undergoing spectacular advances. Machine perfusion is now used in common practice for abdominal and thoracic organ transportation and preservation, and early results are in favor of substantially improved outcomes. It is based on decreasing ischemia-reperfusion phenomena by providing physiological or sub-physiological conditions until transplantation. Alternatively, supercooling techniques involving static preservation at negative temperatures while avoiding ice formation have shown encouraging results in solid organs. Here, the rationale is to decrease the organ's metabolism and need for oxygen and nutrients, allowing for extended preservation durations. The aim of this work is to review all advances of supercooling in transplantation, browsing the literature for each organ. A specific objective was also to study the initial evidence, the prospects, and potential applications of supercooling preservation in Vascularized Composite Allotransplantation (VCA). This complex entity needs a substantial effort to improve long-term outcomes, marked by chronic rejection. Improving preservation techniques is critical to ensure the favorable evolution of VCAs, and supercooling techniques could greatly participate in these advances.

VCA supercooling in a swine partial hindlimb model

“…The sub-zero temperature reduction, combined with the absence of ice nucleation, has been shown to extend liver preservation to 96 hours 50 . Hence, developing a relevant VCA supercooling protocol appears worthwhile 51 . We aimed for 48 h of preservation since this duration would make it possible to combine with immune tolerance protocols based on mixed chimerism.…”

Machine Perfusion Enables 24-h Preservation of Vascularized Composite Allografts in a Swine Model of Allotransplantation

“…Low-temperature preservation has the potential to mitigate cell metabolism, therefore suggesting longer preservation durations [30]. Subzero preservation techniques seem to be promising alternatives for multi-day preservation of solid organs [31][32][33][34][35], but solid evidence still needs to be demonstrated in VCA. In the realm of Normothermic Machine Perfusion (NMP), Fahradyan et al [36] demonstrated 12-h preservation of porcine VCAs with preserved weight and muscle contractility.…”

Sub-Zero Non-Freezing of Vascularized Composite Allografts Preservation in Rodents

“…Preservation techniques enabling organ banking have been developed for liver, kidney, lung and heart models. However, a reliable storage protocol for VCAs allowing for extended storage is lacking [13].…”