Adding the oxygen carrier M101 to a cold-storage solution could be an alternative to HOPE for liver graft preservation

Abstract

Background & Aims: Hypothermic oxygenated machine perfusion (HOPE) is a promising technique for providing oxygen to the liver during graft preservation; however, because of associated logistical constraints, addition of an oxygen transporter to static cold-storage solutions (SCS) might be easier. M101 is marine worm haemoglobin that has been shown to improve kidney preservation in the clinic when added to SCS. This study evaluated the effects of the addition of M101 to SCS on the quality of pig liver graft preservation. Methods: Pig liver grafts were preserved using SCS, HOPE, or SCS+M101, and the liver functions were compared during cold preservation and after orthotopic allotransplantation (OLT) in pigs. Results: During preservation of the liver grafts, mitochondrial function, ATP synthesis, antioxidant capacities, and hepatocyte architecture were better preserved, and free radical production, antioxidant activities, and inflammatory mediators were lower, with HOPE or SCS+M101 than with SCS alone. However, after 1 h of preservation, liver functions with HOPE were superior to those with SCS+M101. After 6 h of preservation and OLT, blood levels of aspartate and alanine aminotransferases and lactate dehydrogenase increased with a peak effect at Day 1 post-transplant; values were similar with HOPE and SCS+M101, and were significantly lower than those in the SCS group. At Days 1 and 3, tumor necrosis factor a levels remained lower with HOPE and SCS+M101 vs. SCS. At Day 7, liver cell necrosis and inflammation were less marked in both oxygenated groups. Conclusions: When added to SCS, M101 effectively oxygenates liver grafts during preservation, preventing post-transplant injury; although graft performances are below those achieved with HOPE.

Oxygen Transport during Ex Situ Machine Perfusion of Donor Livers Using Red Blood Cells or Artificial Oxygen Carriers

“…The initial transplantation-related research was performed by Thuillier et al They demonstrated that Hemarina M101 has a beneficial effect during SCS before kidney transplantation by decreasing chronic fibrosis and organ dysfunction [ 82 ]. Alix et al compared SCS solution with Hemarina M101 versus SCS solution alone during porcine liver graft preservation, showing higher ATP levels in the SCS with Hemarina M101 group after 80 min [ 42 , 83 ]. M101 was also used in preclinical trials as an additive to the perfusion solution during HMP in a marginal kidney porcine model.…”

“…The [42,83]. M101 was also used in preclinical trials as an additive to the perfusion solution during HMP in a marginal kidney porcine model.…”

The importance of adequate oxygenation during hypothermic machine perfusion

“…With interest we have read the recent article by Alix et al describing the effect of M101 (a marine worm hemoglobin) added to the static cold storage (SCS) solution for liver preservation. 1 In this study, the authors compared preservation of porcine liver grafts with SCS supplemented with M101 to SCS alone, or with hypothermic oxygenated machine perfusion (HOPE), followed by transplantation. The authors claim that adding the oxygen carrier M101 to SCS could be an alternative to HOPE for liver graft preservation.…”

Quality and reproducibility during the COVID-19 pandemic

“…In this issue, Alix et al compared the addition of an oxygen carrier (M101) to SCS with SCS alone and the HOPE device in a pig model of liver transplantation. 13 They observed that SCS + M101 and HOPE were better than SCS alone in different preservation parameters (oxidative stress, inflammatory mediators). After 1 hour of preservation, HOPE seemed to be better than SCS + M101.…”