Characteristics of Extracellular Vesicles in Red Blood Concentrates Change with Storage Time and Blood Manufacturing Method

Almizraq, Ruqayyah J.; Holovati, Jelena L.; Acker, Jason P.

doi:10.1159/000486137

Cited by 44 publications

(63 citation statements)

References 60 publications

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“…Lastly, we aimed to assess the utility of plasma vesicles as inflammation and hemolysis markers in patients undergoing CPB. Microvesicle counts, for example in packed red blood cells, seems to correlate with occurring hemolysis acting as quality indicator [22]. Thus, using correlation analysis, we found no significant association between inflammatory markers and hemolysis marker in our patients, nor a difference in the use of packed red blood cells and inotropic drugs.…”

Section: Discussioncontrasting

confidence: 48%

Influence of hemoadsorption during cardiopulmonary bypass on blood vesicle count and function

et al. 2020

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Background Extracorporeal circulation during major cardiac surgery triggers a systemic inflammatory response affecting the clinical course and outcome. Recently, extracellular vesicle (EV) research has shed light onto a novel cellular communication network during inflammation. Hemoadsorption (HA) systems have shown divergent results in modulating the systemic inflammatory response during cardiopulmonary bypass (CPB) surgery. To date, the effect of HA on circulating microvesicles (MVs) in patients undergoing CPB surgery is unknown. Methods Count and function of MVs, as part of the extracellular vesicle fraction, were assessed in a subcohort of a single-center, blinded, controlled study investigating the effect of the CytoSorb device during CPB. A total of 18 patients undergoing elective CPB surgery with (n = 9) and without (n = 9) HA device were included in the study. MV phenotyping and counting was conducted via flow cytometry and procoagulatory potential was measured by tissue factor-dependent MV assays. Results Both study groups exhibited comparable counts and post-operative kinetics in MV subsets. Tissue factor-dependent procoagulatory potential was not detectable in plasma at any timepoint. Post-operative course and laboratory parameters showed no correlation with MV counts in patients undergoing CPB surgery. Conclusion Additional artificial surfaces to the CPB-circuit introduced by the use of the HA device showed no effect on circulating MV count and function in these patients. Larger studies are needed to assess and clarify the effect of HA on circulating vesicle counts and function. Trial registration ClinicalTrials.Gov Identifier: NCT01879176; registration date: June 17, 2013; https://clinicaltrials.gov/ct2/show/NCT01879176

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Section: Discussioncontrasting

confidence: 48%

Influence of hemoadsorption during cardiopulmonary bypass on blood vesicle count and function

et al. 2020

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“…In our study, protease treatment did not affect the thrombogenicity of rbcEVs or pEVs. It should be noted, however, that the rbcEVs used in the studies by Rubin et al (2010); Gao et al (2013), and Noubouossie et al (2020) were derived from red blood cell units that had been stored for 42-45 days, which is likely associated with oxidative changes and storage lesion (D'Alessandro et al, 2015;Almizraq et al, 2018). This enhanced thrombogenicity upon prolonged storage of red blood cell units may also be the cause of a higher incidence of deep vein thrombosis after transfusion of aged blood units (Koch et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Derived From Platelets, Red Blood Cells, and Monocyte-Like Cells Differ Regarding Their Ability to Induce Factor XII-Dependent Thrombin Generation

Tripisciano

Weiss

George

et al. 2020

Front. Cell Dev. Biol.

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As transmitters of biological information, extracellular vesicles (EVs) are crucial for the maintenance of physiological homeostasis, but also contribute to pathological conditions, such as thrombotic disorders. The ability of EVs to support thrombin generation has been linked to their exposure of phosphatidylserine, an anionic phospholipid that is normally restricted to the inner leaflet of the plasma membrane but exposed on the outer leaflet during EV biogenesis. Here, we investigated whether EVs of different cellular origin and from different settings, namely platelets and red blood cells from blood bank units and a monocyte-like cell line (THP-1), differ regarding their potential to support factor XII-dependent thrombin generation. EVs were isolated from blood products or THP-1 cell culture supernatants using differential centrifugation and characterized by a combination of flow cytometry, nanoparticle tracking analysis, and Western blotting. Soluble factors co-enriched during the isolation of EVs were depleted from blood-cell derived EV fractions using size exclusion chromatography, while proteins bound to the surface of EVs were degraded by mild protease treatment. We found that platelet-derived and red blood cell-derived EVs supported factor XII-dependent thrombin generation to comparable extents, while monocytic EVs failed to support thrombin generation when added to EV-depleted human plasma. We excluded a major contribution of co-enriched soluble proteins or of proteins bound to the EV surface to the thrombogenicity of blood cell-derived EVs. Our data suggest that the enhanced potential of blood cell-derived EVs to support thrombin generation is rather due to enhanced exposure of phosphatidylserine on the surface of blood cell-derived EVs. Extending these investigations to EVs from other cell types, such as mesenchymal stromal cells, will be crucial for their future therapeutic applications.

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“…Quantification and size characterization of EVs in RCC were measured using a tunable resistive pulse sensing instrument (TRPS/qNano system; IZON Science Ltd) as previously described in detail. 35,36 Two different nanopores (NP200 and NP400) were used in this study to target EVs ,1 mm in size using a standard stretch range (43-47 mm). Carboxylate polystyrene calibration particles (CPC200; IZON Science Ltd) were used with the NP200 to characterized EVs ,200 nm in diameter, whereas CPC500 (IZON Science Ltd) was used with NP400 nanopore to calibrate for EVs $200 nm.…”

Section: Extracellular Vesicle Characterizationmentioning

confidence: 99%

Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity

et al. 2018

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Transfusion of red cell concentrates (RCCs) is associated with increased risk of adverse outcomes that may be affected by different blood manufacturing methods and the presence of extracellular vesicles (EVs). We investigated the effect of different manufacturing methods on hemolysis, residual cells, cell-derived EVs, and immunomodulatory effects on monocyte activity. Thirty-two RCC units produced using whole blood filtration (WBF), red cell filtration (RCF), apheresis-derived (AD), and whole blood-derived (WBD) methods were examined (n = 8 per method). Residual platelet and white blood cells (WBCs) and the concentration, cell of origin, and characterization of EVs in RCC supernatants were assessed in fresh and stored supernatants. Immunomodulatory activity of RCC supernatants was assessed by quantifying monocyte cytokine production capacity in an in vitro transfusion model. RCF units yielded the lowest number of platelet and WBC-derived EVs, whereas the highest number of platelet EVs was in AD (day 5) and in WBD (day 42). The number of small EVs (<200 nm) was greater than large EVs (≥200 nm) in all tested supernatants, and the highest level of small EVs were in AD units. Immunomodulatory activity was mixed, with evidence of both inflammatory and immunosuppressive effects. Monocytes produced more inflammatory interleukin-8 after exposure to fresh WBF or expired WBD supernatants. Exposure to supernatants from AD and WBD RCC suppressed monocyte lipopolysaccharide-induced cytokine production. Manufacturing methods significantly affect RCC unit EV characteristics and are associated with an immunomodulatory effect of RCC supernatants, which may affect the quality and safety of RCCs.

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Characteristics of Extracellular Vesicles in Red Blood Concentrates Change with Storage Time and Blood Manufacturing Method

Cited by 44 publications

References 60 publications

Influence of hemoadsorption during cardiopulmonary bypass on blood vesicle count and function

Influence of hemoadsorption during cardiopulmonary bypass on blood vesicle count and function

Extracellular Vesicles Derived From Platelets, Red Blood Cells, and Monocyte-Like Cells Differ Regarding Their Ability to Induce Factor XII-Dependent Thrombin Generation

Blood manufacturing methods affect red blood cell product characteristics and immunomodulatory activity

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