So to summarize, selleck chemicals to which extent EVs contain truly distinct types of vesicles requires further investigation, and at present no tools are available to purify a single type or population of vesicle based on size or density.3 EVs expose tissue/cell type-specific marker proteins of their parent cell.[3], [4] and [44] When a sufficient number of such marker proteins are exposed, the cellular origin of a vesicle can be determined

by e.g. flow cytometry using antibodies directed against such marker proteins. This is illustrated in Table 2, in which a shortlist of commonly used marker proteins is summarized for analysis of vesicles in human blood (CD: cluster of differentiation). The numbers, cellular origin, composition and functional properties of EVs are not only disease (state) dependent, but also depend on the body fluids being studied. The major populations of EVs in a body fluid usually reflect the cells that are present in that particular body fluid and that surround the body fluid. Examples of the latter are vesicles from synoviocytes which are present in joint (synovial) fluid, and vesicles from endothelial cells (ECs) in blood. We will briefly summarize the cellular origin presence of EVs in blood, urine, saliva, cerebrospinal and synovial fluids in the following paragraphs. In peripheral blood of a healthy subject, platelets and erythrocytes

are the major sources of EVs, but in certain disease states such as sepsis, cardiovascular disease (CVD), or cancer, also MVs from monocytes, granulocytes, lymphocytes, ECs, and cancer cells can be present.45 Peripheral blood also contains exosomes,46 although the cellular Ku-0059436 order origin of these vesicles is unknown. Urine of healthy humans and amniotic fluid both

contain significant numbers of exosomes or exosome-like vesicles.47 These exosomes expose CD24 and aquaporin-2, therefore, are likely to originate from kidney cells48 and from epithelial cells tetracosactide facing the renal tubule lumen.49 Urine contains also larger vesicles, but thus far the characterization of these two types of vesicles in urine has been problematic.50 In saliva from healthy individuals, the larger vesicles, MVs, are derived mainly from epithelial cells and granulocytes, whereas the smaller vesicles, i.e. exosomes or vesicles resembling exosomes, are mainly from epithelial cell origin.51 Cerebrospinal fluid also contains EVs.52 In vitro, various types of brain cells such as astrocytes, microglia, oligodendrocytes and neurons release exosomes.53 The source of the EVs in cerebrospinal fluid, however, is presently unknown. Synovial fluid of rheumatoid arthritis (RA) patients and patients with other types of arthritis contain MVs.[18] and [54] Most of these MVs originate from cells associated with inflammation, such as monocytes and granulocytes. In addition, synovial fluid also contains vesicles from synovial fibroblasts.55 Taken together, every body fluid has a clearly distinct vesicle profile.