RNA-containing Exosomes in Human Nasal Secretions

Lässer, Cecilia; O’Neil, Serena; Ekerljung, Linda; Ekström, Karin M.; Sjöstrand, Margareta; Lötvall, Jan

doi:10.2500/ajra.2011.25.3573

Cited by 85 publications

(78 citation statements)

References 29 publications

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“…While the majority of microRNAs are found and mediate their regulatory effects on gene expression intracellularly, a number of microRNAs are also present in the extracellular milieu and in various biological fluids of the human body, such as maternal milk [34][35][36][37][38], saliva [39,40], urine [41], nasal secretions [42,43], sperm [44] and plasma [45][46][47][48], and may represent interesting biomarkers of diseases [49,50].…”

Section: Extracellular Micrornas In the Circulationmentioning

confidence: 99%

“…microRNAs are present in all the biological fluids of the human body, such as saliva [39,40], urine [41], nasal secretions [42,43], sperm [44] and plasma [45][46][47][48], which are relatively easy to collect from patients. Can monitoring of platelet-specific MPs and microRNAs in biological samples collected from patients help establish correlations between a given microRNA and specific diseases or conditions, and identify a more sensitive biomarker [89]?…”

Section: Use Of Platelet Mps and Micrornas As Biomarkers Of Diseasementioning

confidence: 99%

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The clinical significance of platelet microparticle-associated microRNAs

Provost

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon vessel wall damage, which is followed by platelet activation, further platelet recruitment, platelet aggregation and formation of an occlusive, or non-occlusive, platelet thrombus. Platelets host a surprisingly diverse transcriptome, which is comprised of ~ 9500 messenger RNAs (mRNAs) and different classes of non-coding RNAs, including microRNAs, as well as a significant repertoire of proteins that contribute to their primary (adhesion, aggregation, granule secretion) and alternative (RNA transfer, mRNA translation, immune regulation) functions. Platelets have the propensity to release microparticles (MPs; 0.1-1 μm in diameter) upon activation, which may mediate inflammatory responses and contribute to exacerbate inflammatory diseases and conditions. Carrying components of the platelets' cytoplasm, platelet MPs may exert their effects on recipient cells by transferring their content in platelet-derived bioactive lipid mediators, cytokines, mRNAs and microRNAs. Platelet MP-associated microRNAs may thus function also outside of platelets and play an important role in intercellular signaling and gene expression programming across the entire circulatory system. The role and importance of platelet MP-associated microRNAs in various aspects of biology and pathophysiology are increasingly recognized, and now provide the scientific basis and rationale to support further translational research and clinical studies. The clinical significance, pathophysiological role as well as the diagnostic and therapeutic potential of platelet MP-associated microRNAs in cardiovascular diseases, platelet transfusion and cancer will be discussed.

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Section: Extracellular Micrornas In the Circulationmentioning

confidence: 99%

Section: Use Of Platelet Mps and Micrornas As Biomarkers Of Diseasementioning

confidence: 99%

The clinical significance of platelet microparticle-associated microRNAs

Provost

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Since the first discovery of exosomes, a wide range of cells have been shown to release these vesicles. Exosomes have also been detected in several biological fluids, including plasma, nasal lavage fluid, saliva and breast milk [3][4][5][6] . Furthermore, it has been demonstrated that the content and function of exosomes depends on the originating cell and the conditions under which they are produced.…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of RNA-Containing Exosomes

Lässer

Eldh

Lötvall

2012

JoVE

Self Cite

383

316

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The field of exosome research is rapidly expanding, with a dramatic increase in publications in recent years. These small vesicles (30-100 nm) of endocytic origin were first proposed to function as a way for reticulocytes to eradicate the transferrin receptor while maturing into erythrocytes 1 , and were later named exosomes. Exosomes are formed by inward budding of late endosomes, producing multivesicular bodies (MVBs), and are released into the environment by fusion of the MVBs with the plasma membrane 2 . Since the first discovery of exosomes, a wide range of cells have been shown to release these vesicles. Exosomes have also been detected in several biological fluids, including plasma, nasal lavage fluid, saliva and breast milk [3][4][5][6] . Furthermore, it has been demonstrated that the content and function of exosomes depends on the originating cell and the conditions under which they are produced. A variety of functions have been demonstrated for exosomes, such as induction of tolerance against allergen 7,8 , eradication of established tumors in mice 9 , inhibition and activation of natural killer cells [10][11][12] , promotion of differentiation into T regulatory cells . Year 2007 we demonstrated that exosomes released from mast cells contain messenger RNA (mRNA) and microRNA (miRNA), and that the RNA can be shuttled from one cell to another via exosomes. In the recipient cells, the mRNA shuttled by exosomes was shown to be translated into protein, suggesting a regulatory function of the transferred RNA 16. Further, we have also shown that exosomes derived from cells grown under oxidative stress can induce tolerance against further stress in recipient cells and thus suggest a biological function of the exosomal shuttle RNA 17. Cell culture media and biological fluids contain a mixture of vesicles and shed fragments. A high quality isolation method for exosomes, followed by characterization and identification of the exosomes and their content, is therefore crucial to distinguish exosomes from other vesicles and particles. Here, we present a method for the isolation of exosomes from both cell culture medium and body fluids. This isolation method is based on repeated centrifugation and filtration steps, followed by a final ultracentrifugation step in which the exosomes are pelleted. Important methods to identify the exosomes and characterize the exosomal morphology and protein content are highlighted, including electron microscopy, flow cytometry and Western blot. The purification of the total exosomal RNA is based on spin column chromatography and the exosomal RNA yield and size distribution is analyzed using a Bioanalyzer.

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“…On the other hand, exosomes originate from the inward budding of early and late endosomes hence forming MVBs containing ILVs [21,22]. Subsequently, the MVBs are transported to and fuse with the plasma membrane, requiring a dynamic interplay between members of the Rab and SNARE protein family, concurrently releasing the ILVs in the extracellular space [23][24][25][26][27]. Partly because both biogenesis pathway are analogous, to date there is no defined panel of markers to distinguish between both vesicle subtypes in a vesicular isolate.…”

Section: Biogenesis Cargo Loading and Compositionmentioning

confidence: 99%

“…EVs have been isolated from e.g. urine [11], plasma [26], semen [25], nasal secretion [24], breast milk [221], the aqueous humor of eyes [222], cerebrospinal fluid [223], peritoneal fluid [224], bronchoalveolar lavage [225]. Depending on the respective disease for which the biomarker is being developed, an accessible biofluid should be considered in which the EVs of interest are likely the most concentrated and a liquid biopsy can be easily obtained.…”

Section: 2evs As Biomarkermentioning

confidence: 99%

Therapeutic and diagnostic applications of extracellular vesicles

Stremersch

Smedt

Raemdonck

2016

Journal of Controlled Release

157

103

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During the past two decades, extracellular vesicles (EVs) have been identified as important mediators of intercellular communication, enabling the functional transfer of bioactive molecules from one cell to another. Consequently, it is becoming increasingly clear that these vesicles are involved in many (patho)physiological processes, providing opportunities for therapeutic applications. Moreover, it is known that the molecular composition of EVs reflects the physiological status of the producing cell and tissue, rationalizing their exploitation as biomarkers in various diseases. In this review the composition, biogenesis and diversity of EVs is discussed in a therapeutic and diagnostic context. We describe emerging therapeutic applications, including the use of EVs as drug delivery vehicles and as cell-free vaccines, and reflect on future challenges for clinical translation. Finally, we discuss the use of EVs as a biomarker source and highlight recent studies and clinical successes.

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RNA-containing Exosomes in Human Nasal Secretions

Cited by 85 publications

References 29 publications

The clinical significance of platelet microparticle-associated microRNAs

The clinical significance of platelet microparticle-associated microRNAs

Isolation and Characterization of RNA-Containing Exosomes

Therapeutic and diagnostic applications of extracellular vesicles

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