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Reduced deformability of stored red blood cells is associated with generation of extracellular vesicles
Institution:1. Keenan Research Centre for Biomedical Science, St. Michael''s Hospital, Toronto, ON, United States;2. Departments of Physiology and Anesthesia, University of Toronto, Toronto, ON, United States;3. Hospital for Sick Children, Department of Anesthesia and Pain Medicine, United States;4. Department of Physics, Ryerson University, Toronto, ON, United States;5. Departments of Physiology and Surgery, University of Toronto, Toronto, ON, United States;6. Institute of Physiology, Charité-Universitätsmedizin Berlin, Germany;7. Department of Biochemistry, Hebrew University, Faculty of Medicine, Jerusalem, Israel;8. Department of Pediatric Surgery, Hadassah- Hebrew University Hospital, Jerusalem, Israel;9. Blood Bank, Hadassah University Hospital, Jerusalem, Israel;1. Department of Laboratory Medicine, National Medical Center, Seoul, South Korea;2. Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, South Korea;3. Department of Laboratory Medicine, SMG-SNU Boramae Medical Center, Seoul, South Korea;4. Seoul Metropolitan Government Public Cord Blood Bank (Allcord), Seoul, South Korea;1. Department of Biotechnology, BK21 Plus Program, Graduate School of Life Sciences and Biotechnology, Department of Food Bioscience and Technology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Republic of Korea;2. HOLISTICBIO, Pangyoyeok-ro, Bundang-gu, Gyeonggi-do, Republic of Korea;3. Dongguk University Research Institute of Biotechnology and Medical Converged Science, Goyang-si, Gyeonggi-do, Republic of Korea;1. Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea;2. Seegene Medical Foundation, Seoul, Republic of Korea;3. Department of Laboratory Medicine, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea;4. Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Republic of Korea;5. Department of Obstetrics and Gynecology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Republic of Korea;1. High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001, PR China;2. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China;3. Qinghai Provincial People''s Hospital, Xining 810007, PR China;4. Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China;5. School of Nursing, Jilin University, Changchun, Jilin 130021, PR China
Abstract:Throughout storage, red blood cells (RBCs) undergo detrimental changes in viability and their ability to effectively transport oxygen. RBC storage lesions are mediated, in part, by a progressive loss of cell deformability, and associated with the release of extracellular vesicles (EVs). Accumulation of EVs during the storage of RBCs correlates with a decrease in RBC surface area to volume ratio. Similarly, the loss of RBC-deformability is associated with loss of RBC surface area to volume ratio. In this study we thus tested whether loss of RBC-deformability is associated with increased RBC-EV production during blood storage.EVs obtained by differential centrifugation of stored RBCs (non-leukoreduced non-irradiated or leukoreduced γ-irradiated RBCs stored 35 or 28 days respectively) were enumerated by high-sensitivity flow cytometry. RBC deformability was quantified, using a cell-flow-properties-analyzer, by measuring the median cell elongation ratio (MER) and percentage of low and high deformable cells in the population (%, LDFC, and HDFC, respectively).The number of EVs was inversely correlated with the MER and positively correlated with the %LDFC with both measures showing highly significant logarithmic dependence with EV levels in stored RBCs. Considering how highly deformable cells did not correlate with EV formation as compared with low deformable RBCs we propose that the formation of EVs is a key factor leading to increased RBC-rigidity.
Keywords:Red blood cells  RBC storage  RBC deformability  Extracellular vesicles
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