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The Effects of Liposome Treatment on Red Blood Cells during Hypothermic Storage Open Access


Other title
Hypothermic Storage
Red Blood Cells
Type of item
Degree grantor
University of Alberta
Author or creator
Da Silveira Cavalcante, Luciana
Supervisor and department
Acker, Jason (Laboratory Medicine and Pathology)
Holovati, Jelena (Laboratory Medicine and Pathology)
Examining committee member and department
Ross-Rodriguez, Lisa (Government of Alberta)
Posse de Chaves, Elena (Pharmacology)
Patel, Rakesh (Pathology)
Laboratory Medicine and Pathology
Date accepted
Graduation date
2017-11:Fall 2017
Doctor of Philosophy
Degree level
Red blood cells (RBCs) are the most commonly used components in cell therapy and their transfusion save millions of lives every year. These benefits were only achieved through advances in blood banking storage techniques that guarantee an available supply of blood to support medical emergencies and treatments. Although use of additive solutions extends storage length of RBC units, the quality of stored RBCs progressively decreases during hypothermic storage giving rise to a series of biochemical and biomechanical changes, collectively known as “hypothermic storage lesion” (HSL). Since membrane integrity is an important predictor of RBC survival and function and constitutes one of the targets of HSL, this research has focused on the use of liposomes, synthetic lipid vesicles, to mitigate RBC membrane injury during hypothermic storage. This thesis tested the hypothesis that liposome treatment of stored RBCs would improve in vitro membrane quality resulting in reduced in vitro production of proinflammatory and procoagulant markers and a safe transfusion product in an anemic rat model. Investigations were conducted on several levels, from assessing baseline differences between rat and human RBCs and the effect of blood component manufacturing on rat RBCs to transfusion of liposome treated-RBCs in a rat model and evaluation of the impact of liposome treatment on hypothermic storage lesion and consequent effects on hemorheologic, immune and coagulatory profile of human blood banked RBCs. The work presented here has established a processing method more suitable for use in animal models of transfusion evaluating HSL as well as demonstrated the effect of DOPC liposomes on rat RBC hemorheology and showed for the first time the in vivo effects of transfusing liposome-treated RBCs in an animal model. Furthermore, it has verified the benefit of liposome treatment in human RBCs by fully characterizing the effects of DOPC liposomes on membrane and metabolic in vitro quality parameters in human RBCs during hypothermic storage. Finally, it has produced novel information about the potential effects of DOPC-treated RBCs and supernatants on the immune response using different cell types, a comprehensive cytokine panel and endothelial activation markers, relevant to current understanding of in vivo inflammatory effects. This thesis has advanced the knowledge of transfusion medicine and biopreservation by offering important insights into the effects of liposome treatment as a tool to mitigate HSL in RBCs that might lead to novel research efforts and unveil the potential of liposomes for biopreservation of other clinically relevant cell types.
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
Cavalcante LS, Acker JP, Holovati, JL. Differences in rat and human erythrocytes following blood component manufacturing: The effect of additive solutions. Transfusion Medicine and Hemotherapy 2015; 42(3):150-7. Publisher: Karger.Cavalcante LS, Feng Q, Chin-Yee I, Acker JP, Holovati, JL. Effect of liposome treated red blood cells in an anemic rat model. Journal of Liposome Research, 2017; 27(1):56-63. Publisher: Taylor & Francis.Cavalcante LS, Brach DR, Duong TT, Yeung RS, Acker JP, Holovati, JL. The immune-stimulation capacity of liposome-treated red blood cells. Journal of Liposome Research, 2017; 9:1-9.Publisher: Taylor & Francis.Cavalcante LS, Holovati JL, Acker JP. Chapter 9: Application of liposomes in biopreservation. In: Multiscale Techonologies for Cryomedicine 2016, 301-27. Publisher: World Scientific.

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