The group “Spleen and transfusion” explores the impact of routine red blood cells (RBC) storage in blood banks on their post-transfusion fate in the recipient. The group interests include the identification of mechanisms determining RBC clearance by the spleen in normal physiology and after transfusion.
Specific lab equipments and in house-developed research tools such as imaging flow cytometry (for a powerful exploration of cell morphology), microsphiltration (mimicking spleen filtration), isolated-perfused human spleen model, cell adhesion platform, ektacytometer, flow cytometry and a cell sorter provide for a multi-parametric exploration of the mature RBC properties. In addition, part of our research activity is located at the Imagine Institute (https://www.institutimagine.org/en/olivier-hermine-181) where mouse models are developed to investigate regulatory mechanisms of RBC clearance in vivo.
Pre-transfusion hypothermic storage of RBC concentrates (up to 42 days in France) is accompanied by numerous alterations called storage lesions, which increase with the duration of storage. These lesions are thought to be responsible for the clearance of 5 – 25% of transfused RBCs reducing transfusion effectiveness. We identified a sub-population of storage-induced micro-erythrocytes (SME), that accumulate during storage, reaching a mean proportion of 24% of the entire RBC population at day 42 (Roussel, Dussiot et al., Transfusion, 2017). We demonstrated that SMEs are cleared from the circulation of an ex vivo perfused human spleen or following transfusion in a mouse model of blood banking and transfusion (Roussel, Morel, Dussiot et al., Blood, 2021), making them a useful and quantitative marker of storage lesion predictive of transfusion effectiveness.
The objective of this project is to contribute to the evaluation of current and future storage processes. This field of research is indeed necessary to ensure a safe and efficient supply of RBC concentrates and regulatory or technological evolutions are under study to improve storage quality. Although each RBC concentrate is currently considered to be of equal quality, regardless of the donor or storage time, and can be used in all indications, progress in research would allow transfusion medicine to evolve towards personalized medicine.
During its existence, the RBC circulates in the vascular network of the body. It is therefore constantly subjected to mechanical and osmotic constraints leading to structural modifications of its cellular components. Several alterations are proposed but few are really validated as markers of senescence or trigger of elimination. The study of RBC physiological aging requires to study them in an organism in which they circulate, without undergoing major modifications that could disturb their production, function, aging and elimination. Also, the lifespan of RBCs is shorter in pathologies such as certain hereditary or acquired anemias. To better understand the etiology of these pathologies, it is important to develop the knowledge of the aging and senescence process of RBCs that will lead to their elimination from the circulation in normal situations.
The objective of this project is to identify the intrinsic and extrinsic determinants of RBC clearance at the end of life, in normal physiology, in pathological conditions or after hypothermic storage. Both human and mouse models are currently used to develop this objective.