While prospective clinical trials are currently underway in several countries throughout the world1, the safety and effectiveness of long-stored erythrocyte concentrates have been questioned by controversial retrospective clinical evidence2, 3 and accumulating biochemical investigations4-6. Laboratory investigations have recently highlighted that a significant number of biochemical and mechanical lesions accumulate in erythrocyte concentrates during their storage in the blood bank. These alterations, often referred to as" storage lesions", include:(i) the progressive impairment of cell metabolism, leading to the consumption of high energy phosphate compounds (ATP and 2, 3-diphosphoglycerate) 7;(ii) the accumulation of oxidative stress, resulting in the oxidation8, non-enzymatic glycosylation9, fragmentation or aggregation of the red blood cell (RBC) membrane10-13 and cytosolic proteins14;(iii) the progressive …