Novel method to leukoreduce murine blood for transfusion: how to reduce animal usage

Fischer, Dania; Büssow, Julian; Meybohm, Patrick; Zacharowski, Kai; Jennewein, Carla

doi:10.1111/trf.13335

Cited by 2 publications

(2 citation statements)

References 15 publications

(20 reference statements)

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“…The similarity between the Hb increment observed in a mouse model and in the human study supports the concept that a mouse model of blood banking and transfusion is relevant to explore the impact of anemia on transfusion efficacy. These results extend an existing literature where mouse models have been used to explore the impact of refrigerated storage 23–30 and the role of the recipient's genetic background on the 24 h PTR 31 …”

Section: Discussionsupporting

confidence: 79%

Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients

Casimir,

Colard,

Dussiot

et al. 2023

American J Hematol

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Red blood cells (RBC) transfusion is used to alleviate symptoms and prevent complications in anemic patients by restoring oxygen delivery to tissues. RBC transfusion efficacy, that can be measured by a rise in hemoglobin (Hb) concentration, is influenced by donor‐, product‐, and recipient‐related characteristics. In some studies, severe pre‐transfusion anemia is associated with a greater than expected Hb increment following transfusion but the biological mechanism underpinning this relationship remains poorly understood. We conducted a prospective study in critically ill patients and quantified Hb increment following one RBC transfusion. In a murine model, we investigated the possibility that, in conjunction with the host erythropoietic response, the persistence of transfused donor RBC is improved to maintain a highest RBC biomass. We confirmed a correlation between a greater Hb increment and a deeper pre‐transfusion anemia in a cohort of 17 patients. In the mouse model, Hb increment and post‐transfusion recovery were increased in anemic recipients. Post‐transfusion RBC recovery was improved in hypoxic mice or those receiving an erythropoiesis‐stimulating agent and decreased in those treated with erythropoietin (EPO)‐neutralizing antibodies, suggesting that EPO signaling is necessary to observe this effect. Irradiated recipients also showed decreased post‐transfusion RBC recovery. The EPO‐induced post‐transfusion RBC recovery improvement was abrogated in irradiated or in macrophage‐depleted recipients, but maintained in splenectomized recipients, suggesting a mechanism requiring erythroid progenitors and macrophages, but which is not spleen‐specific. Our study highlights a physiological role of EPO in downregulating post‐transfusion RBC clearance, contributing to maintain a vital RBC biomass to rapidly cope with hypoxemia.

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Section: Discussionsupporting

confidence: 79%

Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients

Casimir,

Colard,

Dussiot

et al. 2023

American J Hematol

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“…RBC were aseptically collected in CPDA, leukoreduced, and stored at 4°C for up to 14 days, as previously reported. 44 For macrophage depletion, mice were intraperitoneally injected with 1mg and 0.5mg of clodronate liposomes (Liposoma), 5 and 2 days before transfusion, respectively. RBC were stained with CFSE (20µM) and washed twice in RPMI.…”

Section: Mouse Blood Banking and Transfusionmentioning

confidence: 99%

Rapid clearance of storage-induced microerythrocytes alters transfusion recovery

Roussel

Morel

Dussiot

et al. 2021

Blood

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The permanent availability of RBC for transfusion depends on refrigerated storage, during which morphologically-altered RBC accumulate. Among those, a subpopulation of small RBC, comprising echinocytes III, sphero-echinocytes, and spherocytes, and defined as "storage-induced micro-erythrocytes" (SME) could be rapidly cleared from the circulation after transfusion. We quantified the proportion of SME in RBC concentrates from healthy human volunteers and assessed their correlation with transfusion recovery. We then investigated the fate of SME upon perfusion through human spleens ex vivo. Finally, we explored where and how SME are cleared in a mouse model of blood storage and transfusion. In healthy human volunteers, high proportions of SME in long-stored RBC concentrates correlated with poor transfusion recoveries. When perfused through human spleens, 15% and 61% of long-stored RBC and SME were cleared in 70 minutes, respectively. High initial proportions of SME also correlated with high retention of RBC by perfused human spleens. In the mouse model, SME accumulated during storage. Transfusion of long-stored RBC displayed reduced post-transfusion recovery, which was mostly due to clearance of SME. Following transfusions of mice, long-stored RBC accumulated predominantly in the spleen, and were ingested mainly by splenic and hepatic macrophages. In macrophage-depleted mice, splenic accumulation and the clearance of SME were delayed and transfusion recovery was improved. In healthy hosts, SME are cleared predominantly by macrophages in the spleen and liver. When this well-demarcated subpopulation of altered RBC is abundant in RBC concentrates, transfusion recovery is diminished. Quantifying SME has the potential to improve blood product quality assessment.

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Novel method to leukoreduce murine blood for transfusion: how to reduce animal usage

Abstract: LR with CD45 microbeads not only reduces animal usage but also provides a more efficacious method regarding posttransfusion red blood cell recovery and, hence, provides a promising alternative to commonly used methods.

Cited by 2 publications

References 15 publications

Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients

Erythropoietin downregulates red blood cell clearance, increasing transfusion efficacy in severely anemic recipients

Rapid clearance of storage-induced microerythrocytes alters transfusion recovery

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