Screening of red blood cells for extracellular vesicle content as a product quality indicator

Acker, Jason P.; Almizraq, Ruqayyah J.; Millar, Daniel; Maurer‐Spurej, Elisabeth

doi:10.1111/trf.14782

Cited by 12 publications

(13 citation statements)

References 35 publications

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“…Regardless of the possible mechanism of the cause-andeffect interaction, the authors of three experimental studies demonstrated a relationship between the concentration of vesicles in a unit of PRBC and red cell deformability (Acker et al, 2018;Almizraq et al, 2018;McVey et al, 2020). It is important to emphasize that in the two cited publications, the studied blood units were prepared using non-identical protocols, and different techniques were implemented to characterize the deformation of erythrocytes.…”

Section: Vesiculation Of Rbc Membranes During Cold Storagementioning

confidence: 99%

Deformability of Stored Red Blood Cells

2021

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Red blood cells (RBCs) deformability refers to the cells’ ability to adapt their shape to the dynamically changing flow conditions so as to minimize their resistance to flow. The high red cell deformability enables it to pass through small blood vessels and significantly determines erythrocyte survival. Under normal physiological states, the RBCs are attuned to allow for adequate blood flow. However, rigid erythrocytes can disrupt the perfusion of peripheral tissues and directly block microvessels. Therefore, RBC deformability has been recognized as a sensitive indicator of RBC functionality. The loss of deformability, which a change in the cell shape can cause, modification of cell membrane or a shift in cytosol composition, can occur due to various pathological conditions or as a part of normal RBC aging (in vitro or in vivo). However, despite extensive research, we still do not fully understand the processes leading to increased cell rigidity under cold storage conditions in a blood bank (in vitro aging), In the present review, we discuss publications that examined the effect of RBCs’ cold storage on their deformability and the biological mechanisms governing this change. We first discuss the change in the deformability of cells during their cold storage. After that, we consider storage-related alterations in RBCs features, which can lead to impaired cell deformation. Finally, we attempt to trace a causal relationship between the observed phenomena and offer recommendations for improving the functionality of stored cells.

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Section: Vesiculation Of Rbc Membranes During Cold Storagementioning

confidence: 99%

Deformability of Stored Red Blood Cells

2021

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“…They concluded that from day 7 to day 42 of storage, the amount of glycophorin A positive and PS positive REVs varied over time and the number of PS positive REVs did not correlate with thrombin formation. Recently, Almizraq and coworkers recommended the extracellular vesicle content as an additional product quality indicator in RBC concentrate screening 11 . Furthermore, they revealed that both the concentration and size-profile of EVs in stored red blood cell units are markedly influenced by blood manufacturing methods, storage time and the method of detection 12 – 14 .…”

Section: Introductionmentioning

confidence: 99%

Storage conditions determine the characteristics of red blood cell derived extracellular vesicles

Bebesi

Kitka

Gaál

et al. 2022

Sci Rep

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Extracellular vesicles (EVs) are released during the storage of red blood cell (RBC) concentrates and might play adverse or beneficial roles throughout the utilization of blood products (transfusion). Knowledge of EV release associated factors and mechanism amends blood product management. In the present work the impact of storage time and medium (blood preserving additive vs isotonic phosphate buffer) on the composition, size, and concentration of EVs was studied using attenuated total reflection infrared (ATR-IR) spectroscopy, microfluidic resistive pulse sensing (MRPS) and freeze-fraction combined transmission electron micrography (FF-TEM). The spectroscopic protein-to-lipid ratio based on amide and the C–H stretching band intensity ratio indicated the formation of various vesicle subpopulations depending on storage conditions. After short storage, nanoparticles with high relative protein content were detected. Spectral analysis also suggested differences in lipid and protein composition, too. The fingerprint region (from 1300 to 1000 cm−1) of the IR spectra furnishes additional information about the biomolecular composition of RBC-derived EVs (REVs) such as adenosine triphosphate (ATP), lactose, glucose, and oxidized hemoglobin. The difference between the vesicle subpopulations reveals the complexity of the REV formation mechanism. IR spectroscopy, as a quick, cost-effective, and label-free technique provides valuable novel biochemical insight and might be used complementary to traditional omics approaches on EVs.

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“…The quality and clinical impact of stored and differentially manufactured red cell concentrates from different donor groups is a major concern, and as exosomes are markers of cellular activation or degradation, a recent study investigated the utility of exosomes screening to characterize the effects of RBCs production methods and storage [ 147 ]. The most used EV isolation methods include ultracentrifugation, density gradient centrifugation, size exclusion chromatography, and polymer-based precipitation, with each varying in yield of EVs, the depletion of lipoproteins and protein contaminants, labor-intensity, and cost of the procedure.…”

Section: Red Blood Cells Extracellular Vesiclementioning

confidence: 99%

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

Sanz-Rubio

2021

IJMS

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Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).

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Screening of red blood cells for extracellular vesicle content as a product quality indicator

Abstract: EV content correlates with measures of hemolysis and other RBC quality indicators and could be implemented as a routine screening tool for nondestructive QC testing of RCCs.

Cited by 12 publications

References 35 publications

Deformability of Stored Red Blood Cells

Deformability of Stored Red Blood Cells

Storage conditions determine the characteristics of red blood cell derived extracellular vesicles

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

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