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. 2022 Jun 8;12(6):803. doi: 10.3390/biom12060803

Table 2.

Red blood cell-derived microvesicles’ source, detection methods, immunophenotypic characteristics, role, and association with diseases progression/initiation/prognosis and potential utility as disease biomarkers.

Red Blood Cell-Derived MVs
MVs Source Isolation/Characterization Method MVs Phenotype Function/Role Disease Effects/Relation to Disease References
Blood plasma Differential centrifugation/Flow Cytometry CD235+ PS+ MVs accumulation Thrombin activation, Nitric Oxide bioavailability disruption Sickle Cell Disease and Thalassaemia Intermedia Potential pro-thrombotic marker [22,74]
Blood plasma Differential centrifugation/Flow Cytometry CD235a+ PS+ MVs accumulation Myeloproliferative neoplasms [29]
Blood plasma Differential centrifugation/Flow Cytometry CD235a+ MVs accumulation Positive correlation with aortic stiffness, pulmonary artery pressure, and tricuspid regurgitant velocity Sickle Cell Disease Potential biomarker for vascular dysfunction and disease severity [30]
TSP-1 stimulated RBCs, isolated from blood Centrifugation/Flow Cytometry CD235a+ PS+ MVs accumulation Endothelial cell damage, vascular dysfunction, renal vaso-occlusion Sickle Cell Disease (mice) [75]
Blood plasma Differential centrifugation/Flow Cytometry CD235a+ PS- and CD235a+ CD59- MVs accumulation Disturbed contribution
to hemostasis and thrombosis
Paroxysmal Nocturnal Hemoglobinuria [76]
Blood plasma Differential centrifugation/Flow Cytometry, Atomic Force Microscopy CD235a+ PS+ MVs accumulation Positive correlation with G6PD enzyme activity G6PD deficiency Potential biomarker of G6PD deficiency severity [77]
Stimulated RBCs, isolated from blood Ultracentrifugation/NTA, Immunoblotting analysis and TEM CD235a+ MVs accumulation Disturbed the homeostasis of vascular tone, hypertension induction Obstructive Sleep Apnea Endothelial dysfunction marker, Obstructive Sleep Apnea severity [78,79]
Blood plasma Differential centrifugation/Flow Cytometry and TEM CD235a+ PS+ MVs accumulation correlation with several coronary artery diseases and adverse clinical events Myocardial Infarction [80,81]
RBCs infected with P. falciparum (cell cultures) Differential centrifugation, filtration, 60% sucrose cushion/Flow cytometry, TEM and Immunoblotting analysis RMVs-derived from Malaria Infected RBCs Immunomodulatory properties, Transmission stage parasite development stimulation Malaria Infection [82]
RBCs infected with P. falciparum (cell cultures) Differential centrifugation/Flow Cytometry, PCR, Immunoblotting analysis Enriched in hAgo2-miRNA complexes RMVs innate resistance of RBCs to malaria infection Malaria Infection Therapeutic potential as drug delivery systems [83,84]
Blood plasma Differential centrifugation/Flow Cytometry, TEM TER-119+ MVs accumulation Cardioprotective effects Ischemic preconditioning [85]
Blood plasma Immuno-capture method/NTA, Immunoblotting analysis and TEM Enriched in a-synuclein CD235a+ MVs Rapid crossing of the blood-brain barrier Parkinson Disease Progression or initiation disease biomarker [86,87]
Blood plasma Differential centrifugation/Flow Cytometry PS+ CD235a+ MVs accumulation Association with hyperlipidemia Metabolic Syndrome [88]

RBCs, red blood cells; G6PD, Glucose-6-phosphate dehydrogenase; NTA, Nanoparticle Tracking Analysis, PCR, Polymerase Chain Reaction; PS, phosphatidyleserine; TEM, Transmission Electron Microscopy.