Efficacy of the natural oxygen transporter HEMO ₂ life ^® in cold preservation in a preclinical porcine model of donation after cardiac death

Abstract

The growing use of marginal organs for transplantation pushes current preservation methods toward their limits, and the need for improvement is pressing. We previously demonstrated the benefits of M101, a natural extracellular oxygen carrier compatible with hypothermia, for the preservation of healthy renal grafts in a porcine model of autotransplantation. Herein, we use a variant of this preclinical model to evaluate M101 potential benefits both in static cold storage (CS) and in machine perfusion (MP) preservation in the transplantation outcomes for marginal kidneys. In the CS arm, despite the absence of obvious benefits within the first 2 weeks of follow-up, M101 dose-dependently improved long-term function, normalizing creatininemia after 1 and 3 months. In the MP arm, M101 improved short-and long-term functional outcomes as well as tissue integrity. Importantly, we provide evidence for the additivity of MP and M101 functional effects, showing that the addition of the compound further improves organ preservation, by reducing short-term function loss, with no loss of function or tissue integrity recorded throughout the follow-up. Extending previous observations with healthy kidneys, the present results point at the M101 oxygen carrier as a viable strategy to improve current organ preservation methods in marginal organ transplantation. Transplant International 2019; 32: 985-996

First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study

“…This protein does not induce mutagenic, immunogenic, or allergenic responses and is degraded into polypeptide chains and heme . The addition of M101 to preservation solution prevents the progressive decline of the dissolved oxygen concentration . The efficacy of M101 used ex vivo as an additive to preservation solutions for preventing ischemia/reperfusion injuries has been demonstrated in preclinical studies in kidney, heart, and lung .…”

A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level

“…With oxygenation, temperature is one key parameter in renal graft preservation. Based on cell metabolic reduction, hypothermic storage is the main strategy to minimize ischemic (and/or reperfusive) injuries [3,99]. RCM hemoglobin stabilizes cortical oxygen and slows the ischemic O 2 disappearance; exploratory experiments where parameters and processes were adjusted at their 4 • C-equivalent showed that low temperature stabilizes tissue oxygen.…”

“…RCM hemoglobin stabilizes cortical oxygen and slows the ischemic O 2 disappearance; exploratory experiments where parameters and processes were adjusted at their 4 • C-equivalent showed that low temperature stabilizes tissue oxygen. Thus RCM could also be used as a helping tool to analyze the role of temperature on the one hand, and hemoglobin and various other oxygen carriers, on the other hand [3,99].…”

Beneficial effects of the novel marine oxygen carrier M101 during cold preservation of rat and human pancreas

“…Efficacy and safety of M101 in organ preservation has been shown to improve graft function for clinical studies on kidney and face transplantation, and for pre‐clinical studies on the kidney, lung and heart . Additionally, its ease of use (the molecule can simply be added to the preservation solution) makes it of interest for cold organ preservation, either under static storage or with machine perfusion …”

“…[21][22][23] Additionally, its ease of use (the molecule can simply be added to the preservation solution) makes it of interest for cold organ preservation, either under static storage or with machine perfusion. 24,25 The goal of the present study was to identify the impact of cold ischaemia on pancreatic islets through examination of the efficacy of M101 on pancreas cold preservation, using both rat and human models.…”