Extracellular vesicles in the circulation: are erythrocyte microvesicles a confounder in the plasma haemoglobin assay?

Vooght, Karen M.K. de; Lau, Cedric; Laat, Pim P.M. de; Wijk, Richard van; Solinge, Wouter W. van; Schiffelers, Raymond M.

doi:10.1042/bst20120254

Cited by 14 publications

(10 citation statements)

References 29 publications

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“…Blood contains a variety of extracellular vesicles released from many different cell types, above all platelets, leukocytes, erythrocytes, and endothelial cells (33). To identify the contribution of GBM-derived extracellular vesicles to the whole circulating extracellular vesicle population, we measured extracellular vesicle concentration in paired pre-and postoperative GBM plasma samples (n ¼ 14).…”

Section: Tumor Cells Are Mainly Responsible For Extracellular Vesiclementioning

confidence: 99%

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients

Osti

Bene

Rappa

et al. 2019

Clinical Cancer Research

209

139

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Purpose: Glioblastoma (GBM) is the most common primary brain tumor. The identification of blood biomarkers reflecting the tumor status represents a major unmet need for optimal clinical management of patients with GBM. Their high number in body fluids, their stability, and the presence of many tumor-associated proteins and RNAs make extracellular vesicles potentially optimal biomarkers. Here, we investigated the potential role of plasma extracellular vesicles from patients with GBM for diagnosis and follow-up after treatment and as a prognostic tool. Experimental Design: Plasma from healthy controls (n ¼ 33), patients with GBM (n ¼ 43), and patients with different central nervous system malignancies (n ¼ 25) were collected. Extracellular vesicles were isolated by ultracentrifugation and characterized in terms of morphology by transmission electron microscopy, concentration, and size by nanoparticle tracking analysis, and protein composition by mass spectrometry. An orthotopic mouse model of human GBM confirmed human plasma extracellular vesicle quantifications. Associations between plasma extracellular vesicle concentration and clinicopathologic features of patients with GBM were analyzed. All statistical tests were two-sided. Results: GBM releases heterogeneous extracellular vesicles detectable in plasma. Plasma extracellular vesicle concentration was higher in GBM compared with healthy controls (P < 0.001), brain metastases (P < 0.001), and extra-axial brain tumors (P < 0.001). After surgery, a significant drop in plasma extracellular vesicle concentration was measured (P < 0.001). Plasma extracellular vesicle concentration was also increased in GBM-bearing mice (P < 0.001). Proteomic profiling revealed a GBM-distinctive signature. Conclusions: Higher extracellular vesicle plasma levels may assist in GBM clinical diagnosis: their reduction after GBM resection, their rise at recurrence, and their protein cargo might provide indications about tumor, therapy response, and monitoring.

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Section: Tumor Cells Are Mainly Responsible For Extracellular Vesiclementioning

confidence: 99%

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients

Osti

Bene

Rappa

et al. 2019

Clinical Cancer Research

209

139

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“…Research by others have demonstrated that exosomes (∼50 nm) and microvesicles (∼200 nm) from endothelial cells, leukocytes, and platelets exceed the amount of RBC EVs (i.e., microvesicles) in the plasma of healthy individuals (blood donors) [25] as well as in blood bank-produced RCCs as they enter storage [26]. While we did not look at non-RBC EVs in this study, this prior work led us to postulate that the average size increase of the RCC EVs during storage reflected the accumulation of RBC EVs (microvesicles) over exosomes (non-RBC origin) caused by the RBC vesiculation.…”

Section: Discussionmentioning

confidence: 99%

Blood Bag Plasticizers Influence Red Blood Cell Vesiculation Rate without Altering the Lipid Composition of the Vesicles

Bicalho

Serrano

Pereira

et al. 2015

Transfus Med Hemother

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Background: Polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate (DEHP) is commonly used for blood collection and storage. DEHP has protective effects on RBC membranes, but is also a toxin. Methods: A paired study was conducted to investigate the influence of DEHP and two alternative plasticizers, 1,2-cyclohexane-dicarboxylic acid diisononyl ester (DINCH) and n-butyryl-tri-n-hexyl citrate (BTHC), on the preservation of RBCs stored for 42 days in PVC pediatric bags. The RBC membrane was evaluated for supernatant hemoglobin (Hb), release of extracellular microvesicles (EVs), osmotic fragility, deformability, and lipid composition. Results: In BTHC-plasticized bags, the supernatant Hb increase during storage was 2 times greater than in DINCH- and DEHP-plasticized bags. By day 21, EV concentrations had doubled from day-5 levels in DINCH- and DEHP-, and trebled in BTHC-plasticized bags. RBC mean cell volumes were greater in BTHC- than in DINCH- or DEHP-plasticized bags (p < 0.001). Osmotic fragility differed significantly among plasticizers (p < 0.01). After day 21, RBC deformability decreased in all, but to a greater extent in the bags with BTHC. Phospholipid composition of RBCs and EVs was not different among plasticizers. Conclusion: Membrane stabilization capacity differed among the plasticizers. RBC in BTHC bags stored more poorly, while DEHP and DINCH bags offered better protection against vesiculation, osmotic stress, and Hb loss.

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“…Later, in 1983, two independent groups reported the release of extracellular vesicles by exocytosis of multivesicular endosomes during the maturation of reticulocytes (Harding et al, 1983; Pan and Johnstone, 1983). Although reticulocytes, or immature RBCs, secrete exosomes during the remodeling process that accompanies their maturation, mature RBCs are probably the only cells that do not secrete exosomes and shed only microvesicles (de Vooght et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

Red blood cell vesiculation in hereditary hemolytic anemia

et al. 2013

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Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias.

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Extracellular vesicles in the circulation: are erythrocyte microvesicles a confounder in the plasma haemoglobin assay?

Cited by 14 publications

References 29 publications

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients

Clinical Significance of Extracellular Vesicles in Plasma from Glioblastoma Patients

Blood Bag Plasticizers Influence Red Blood Cell Vesiculation Rate without Altering the Lipid Composition of the Vesicles

Red blood cell vesiculation in hereditary hemolytic anemia

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