Extended supercooled storage of red blood cells

• Published in: Communications biology 2024-06, Vol.7 (1), p.765-9, Article 765
• Main Authors: Isiksacan, Ziya, William, Nishaka, Senturk, Rahime, Boudreau, Luke, Wooning, Celine, Castellanos, Emily, Isiksacan, Salih, Yarmush, Martin L., Acker, Jason P., Usta, O. Berk
• Format: Article
• Language: English
• Subjects: 631/61; 631/80; 692/308; Antioxidants; Antioxidants - metabolism; Biomedical and Life Sciences; Blood; Blood Preservation - methods; Cold Temperature; Cryopreservation - methods; Erythrocytes; Erythrocytes - cytology; Hematocrit; Humans; Life Sciences; Oxidative Stress; Resveratrol; Time Factors; Vitamin E
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06463-4

Red blood cell (RBC) transfusions facilitate many life-saving acute and chronic interventions. Transfusions are enabled through the gold-standard hypothermic storage of RBCs. Today, the demand for RBC units is unfulfilled, partially due to the limited storage time, 6 weeks, in hypothermic storage. This time limit stems from high metabolism-driven storage lesions at +1-6 °C. A recent and promising alternative to hypothermic storage is the supercooled storage of RBCs at subzero temperatures, pioneered by our group. Here, we report on long-term supercooled storage of human RBCs at physiological hematocrit levels for up to 23 weeks. Specifically, we assess hypothermic RBC additive solutions for their ability to sustain supercooled storage. We find that a commercially formulated next-generation solution (Erythro-Sol 5) enables the best storage performance and can form the basis for further improvements to supercooled storage. Our analyses indicate that oxidative stress is a prominent time- and temperature-dependent injury during supercooled storage. Thus, we report on improved supercooled storage of RBCs at −5 °C by supplementing Erythro-Sol 5 with the exogenous antioxidants, resveratrol, serotonin, melatonin, and Trolox. Overall, this study shows the long-term preservation potential of supercooled storage of RBCs and establishes a foundation for further improvement toward clinical translation. This study explores the premise of extended – up to 23 weeks – supercooled storage of human red blood cells in modern and traditional hypothermic additive solutions and the impact of antioxidant supplementation, in comparison to hypothermic storage.