The oxygen carrier M101 alleviates complement activation, which may be beneficial for donor organ preservation

Puissant‐Lubrano, Bénédicte; Bouthemy, Charlène; Congy‐Jolivet, Nicolas; Milhes, Jean; Minville, Vincent; Kamar, Nassim; Demini, Leïla; Zal, Franck; Renaudineau, Yves

doi:10.3389/fimmu.2022.1006761

Cited by 4 publications

(2 citation statements)

References 35 publications

(50 reference statements)

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“…Animal studies showed that M101 does not bind NO (nitric oxide), nor causes vasoconstriction, and has no immunogenicity, compared with other noncell-bound hemoglobin carriers (15–17). Studies in mice demonstrated an increase in the oxygenation of poorly vascularized tissues (18).…”

Section: Introductionmentioning

confidence: 99%

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Effects of M101—an Extracellular Hemoglobin—applied During Cardiopulmonary Resuscitation: An Experimental Rodent Study

Iten

Glas

Kindler

et al. 2023

Shock

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During and immediately after cardiac arrest, cerebral oxygen delivery is impaired mainly by microthrombi and cerebral vasoconstriction. This may narrow capillaries so much that it might impede the flow of red blood cells and thus oxygen transport. The aim of this proof-of-concept study was to evaluate the effect of M101, an extracellular hemoglobin-based oxygen carrier (Hemarina SA, Morlaix, France) derived from Arenicola marina, applied during cardiac arrest in a rodent model, on markers of brain inflammation, brain damage, and regional cerebral oxygen saturation. Twenty-seven Wistar rats subjected to 6 min of asystolic cardiac arrest were infused M101 (300 mg/kg) or placebo (NaCl 0.9%) concomitantly with start of cardiopulmonary resuscitation. Brain oxygenation and five biomarkers of inflammation and brain damage (from blood, cerebrospinal fluid, and homogenates from four brain regions) were measured 8 h after return of spontaneous circulation. In these 21 different measurements, M101-treated animals were not significantly different from controls except for phospho-tau only in single cerebellum regions ( P = 0.048; ANOVA of all brain regions: P = 0.004). Arterial blood pressure increased significantly only at 4 to 8 min after return of spontaneous circulation ( P < 0.001) and acidosis decreased ( P = 0.009). While M101 applied during cardiac arrest did not significantly change inflammation or brain oxygenation, the data suggest cerebral damage reduction due to hypoxic brain injury, measured by phospho-tau. Global burden of ischemia appeared reduced because acidosis was less severe. Whether postcardiac arrest infusion of M101 improves brain oxygenation is unknown and needs to be investigated.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of M101—an Extracellular Hemoglobin—applied During Cardiopulmonary Resuscitation: An Experimental Rodent Study

Iten

Glas

Kindler

et al. 2023

Shock

View full text Add to dashboard Cite

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Type I interferon associated epistasis may contribute to early disease-onset and high disease activity in juvenile-onset lupus

Renaudineau,

Charras,

Natoli

et al. 2024

Clinical Immunology

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Oxygen carriers affect kidney immunogenicity during ex-vivo machine perfusion

Rother,

Horgby,

Schmalkuche

et al. 2023

Front. Transplant.

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Normothermic ex-vivo machine perfusion provides a powerful tool to improve donor kidney preservation and a route for the delivery of pharmacological or gene therapeutic interventions prior to transplantation. However, perfusion at normothermic temperatures requires adequate tissue oxygenation to meet the physiological metabolic demand. For this purpose, the addition of appropriate oxygen carriers (OCs) to the perfusion solution is essential to ensure a sufficient oxygen supply and reduce the risk for tissue injury due to hypoxia. It is crucial that the selected OCs preserve the integrity and low immunogenicity of the graft. In this study, the effect of two OCs on the organ's integrity and immunogenicity was evaluated. Porcine kidneys were perfused ex-vivo for four hours using perfusion solutions supplemented with red blood cells (RBCs) as conventional OC, perfluorocarbon (PFC)-based OC, or Hemarina-M101 (M101), a lugworm hemoglobin-based OC named HEMO2life®, recently approved in Europe (i.e., CE obtained in October 2022). Perfusions with all OCs led to decreased lactate levels. Additionally, none of the OCs negatively affected renal morphology as determined by histological analyses. Remarkably, all OCs improved the perfusion solution by reducing the expression of pro-inflammatory mediators (IL-6, IL-8, TNFα) and adhesion molecules (ICAM-1) on both transcript and protein level, suggesting a beneficial effect of the OCs in maintaining the low immunogenicity of the graft. Thus, PFC-based OCs and M101 may constitute a promising alternative to RBCs during normothermic ex-vivo kidney perfusion.

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The oxygen carrier M101 alleviates complement activation, which may be beneficial for donor organ preservation

Cited by 4 publications

References 35 publications

Effects of M101—an Extracellular Hemoglobin—applied During Cardiopulmonary Resuscitation: An Experimental Rodent Study

Effects of M101—an Extracellular Hemoglobin—applied During Cardiopulmonary Resuscitation: An Experimental Rodent Study

Type I interferon associated epistasis may contribute to early disease-onset and high disease activity in juvenile-onset lupus

Oxygen carriers affect kidney immunogenicity during ex-vivo machine perfusion

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