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

  • Author / Creator
    Da Silveira Cavalcante, Luciana
  • 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.

  • Subjects / Keywords
  • Graduation date
    2017-11:Fall 2017
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3N873D18
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. 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.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Laboratory Medicine and Pathology
  • Specialization
    • Biopreservation
  • Supervisor / co-supervisor and their department(s)
    • Holovati, Jelena (Laboratory Medicine and Pathology)
    • Acker, Jason (Laboratory Medicine and Pathology)
  • Examining committee members and their departments
    • Posse de Chaves, Elena (Pharmacology)
    • Patel, Rakesh (Pathology)
    • Ross-Rodriguez, Lisa (Government of Alberta)