The DOI matches its Crossref record; 126 of the 126 references it cites were found in a registry or an index; 25 of the 47 sources its claims cite were checked for support.
Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies
Open accessAbstract
Recent studies suggest both normal and cancerous cells secrete vesicles into the extracellular space. These extracellular vesicles (EVs) contain materials that mirror the genetic and proteomic content of the secreting cell. The identification of cancer-specific material in EVs isolated from the biofluids (e.g., serum, cerebrospinal fluid, urine) of cancer patients suggests EVs as an attractive platform for biomarker development. It is important to recognize that the EVs derived from clinical samples are likely highly heterogeneous in make-up and arose from diverse sets of biologic processes. This article aims to review the biologic processes that give rise to various types of EVs, including exosomes, microvesicles, retrovirus like particles, and apoptotic bodies. Clinical pertinence of these EVs to neuro-oncology will also be discussed.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Extracellular vesicles (EVs) are a heterogeneous mix of exosomes, microvesicles, retrovirus-like particles, and apoptotic bodies that differ in biogenesis, size, and marker profile. The review argues that these differences matter for neuro-oncology biomarker and therapeutic development, while current isolation and marker definitions remain imperfect.
Key findings
- EVs arise through distinct routes: exosomes from endosomal multivesicular bodies, microvesicles from outward plasma membrane budding, retrovirus-like particles from retroviral protein-driven budding, and apoptotic bodies from programmed cell death.
- Reported size ranges overlap: exosomes are 30–100 nm, microvesicles 50–2000 nm, retrovirus-like particles 90–100 nm, and apoptotic bodies 500–4000 nm, with smaller 50–500 nm vesicles also released during apoptosis.
- Candidate markers include CD63/CD9 for exosomes, ARF6 and VAMP3 for microvesicles, Gag for retrovirus-like particles, and thrombospondin/C3b for apoptotic bodies, but the review notes that marker sensitivity and specificity have not been carefully validated.
- Clinically, EV cargo can protect tumor-derived RNA and protein, and examples include detection of EGFRvIII, IDH-1, and c-myc; a microfluidic μNMR device detected glioblastoma-associated proteins with sensitivity orders of magnitude above Western blotting and ELISA and tracked clinical response in serial serum samples.
Methods
- Narrative review of published literature on EV biogenesis, isolation, surface markers, and clinical applications, with emphasis on neuro-oncology.
- Synthesizes cell biology studies, marker studies, and clinical biomarker/therapeutic reports rather than presenting new experimental data.
- No systematic search strategy or primary sample collection is described.
Limitations
- The paper states that EV terminology is not standardized, that marker studies were largely performed in non-neoplastic cell lines, and that biogenesis remains incompletely understood; ESCRT-independent exosomes may lack standard markers such as CD63 or CD9.
- The paper states that tumor-derived EVs are a small minority among biofluid EVs, creating sensitivity challenges, and that current isolation often relies on size/density or CD63, which may not be specific to one EV type.
- Evident from the text: as a narrative review, it does not provide primary data or a systematic methodology, and its proposed marker schema requires further validation.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
11 Partly supported · 6 Own interpretation · 4 No full text of the sources · 2 Supported · 1 Sources not found · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These vesicles are secreted by both normal cells and cancerous cells as means of cell-to-cell communication [2-5].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Introduction
What the sources say
- Partly supportedcites [2] Raposo G et al (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183(3):1161–1172 sourceExperimental — accuracy not yet measured
The Results (p. 1165) show that exosomes released by B-cell lines stimulated T cells, supporting a form of cell-to-cell signaling. The Materials and Methods identify the human B-cell lines as EBV-transformed, while the Discussion (p. 1169) reports only preliminary observations of exosomes on physiological immune cells and says their role in vivo remains to be established. The paper does not establish the broad claim that both normal and cancerous cells secrete vesicles as a means of communication. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [3] Blanchard N et al (2002) TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol 168(7):3235–3241 source
- Not checked — no full text of the sourcecites [4] Andre F et al (2004) Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J Immunol 172(4):2126–2136 source
- Supportedcites [5] Taylor DD, Akyol S, Gercel-Taylor C (2006) Pregnancy-associated exosomes and their modulation of t cell signaling. J Immunol 176(3):1534–1542 source
The Discussion (page not provided) describes exosomes as mediating communication between lymphocytes and dendritic cells and reports exosome release by other normal cells. It also reports exosomes isolated from tumor cells that carry antigens and can be processed by dendritic cells, supporting the broad claim for cancerous cells. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the contents of the vesicles released mirror aspects of the secreting cell. [1]”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Introduction
What the sources say
- Supportedcites [1] Skog J et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476 source
The paper’s main text (page not provided) says that microvesicle content depends on the cell of origin. It also reports that microvesicle miRNAs parallel their distribution in the glioblastoma cells that released them, directly supporting the claim that vesicle contents mirror aspects of the secreting cell. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These results suggest that genetic information can also be transferred by uptake of apoptotic bodies.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Apoptotic Bodies
What the sources say
- Supportedcites [114] Bergsmedh A et al (2001) Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc Natl Acad Sci USA 98(11):6407–6411 source
The Abstract states that tumor DNA may be horizontally transferred through uptake of apoptotic bodies. The Discussion reports transfer of activated oncogenes by this route, supporting the claim that genetic information can be transferred this way. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
In the paper
“The mode of biogenesis of exosomes is distinct from vesicles that arise through direct outward budding and fission of the plasma membrane (Figure 4). To distinguish these vesicles by their mode of biogenesis, the latter class of vesicles is frequently referred to as microvesicles [59].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Microvesicles
What the sources say
- Not checked — no full text of the sourcecites [59] Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19(2):43–51 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that RLPs may be a constituent of the EVs isolated from patient biofluids.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Retrovirus-Like Particles (RLPs)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 15
- Probably not a substantial claim. 5
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Work in yeast [28-31] and other tissue culture models [32-34] suggests that ILV formation requires two distinct processes. The first involves the organization of the endosome membrane into specialized units highly enriched for a class of membrane proteins called tetraspanins [35].”
- Also stated in: § Exosomes · plain
“The second step in ILV/exosome formation involves a series of complexes called Endosomal Sorting Complex Required for Transport, or ESCRTs for short. There are four multi-protein complexes required for ILV formation and they are termed ESCRT 0, I, II, and III [39-41].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Exosomes
What the sources say
- Not checked — no full text of the sourcecites [28] Odorizzi G, Babst M, Emr SD (1998) Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell 95(6):847–858 source
- Partly supportedcites [29] Reggiori F, Pelham HRB (2001) Sorting of proteins into multivesicular bodies: ubiquitin-dependent and -independent targeting. EMBO J 20(18):5176–5186 sourceExperimental — accuracy not yet measured
The section 'Identification of proteins in internal vesicles' reports that multivesicular-body formation in yeast is blocked in vps4 mutants. 'Ubiquitylation as a sorting signal in late endosomes' proposes that some cargo partitions into an endosomal membrane domain with different properties. Neither passage establishes that ILV formation requires two distinct processes involving tetraspanin-enriched microdomains and ESCRT complexes; the tetraspanin statement in the citing sentence is separately cited to [35]. (LLM, conf=0.85)
- Partly supportedcites [30] Nickerson DP et al (2010) Regulators of Vps4 ATPase activity at endosomes differentially influence the size and rate of formation of intralumenal vesicles. Mol Biol Cell 21(6):1023–1032 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says ESCRT complexes mediate packaging into intralumenal vesicles, supporting the ESCRT part of the claim. Our copy does not describe tetraspanin-enriched microdomains or establish that ILV formation requires the two distinct processes claimed. In the citing sentence, the tetraspanin-specific statement is separately cited to [35]. (LLM, conf=0.87)
- Partly supportedcites [31] Babst M (2005) A protein’s final ESCRT. Traffic 6(1):2–9 sourceExperimental — accuracy not yet measured
The Abstract (page not supplied) states that ESCRT complexes are required for the formation of multivesicular-body lumenal vesicles. The paper does not identify tetraspanin-enriched microdomains as a second required process; its MVB Vesicle Formation and Dynamics section instead discusses a possible role for lipids in membrane invagination. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [32] Hurley JH, Emr SD (2006) The ESCRT complexes: structure and mechanism of a membrane-trafficking network. Annu Rev Biophys Biomol Struct 35:277–298 source
- Not checked — no full text of the sourcecites [33] Katzmann DJ, Odorizzi G, Emr SD (2002) Receptor downregulation and multivesicular-body sorting. Nat Rev Mol Cell Biol 3(12):893–905 source
- Not checked — no full text of the sourcecites [34] Slagsvold T et al (2006) Endosomal and non-endosomal functions of ESCRT proteins. Trends Cell Biol 16(6):317–326 source
- Not checked — no full text of the sourcecites [35] Pols MS, Klumperman J (2009) Trafficking and function of the tetraspanin CD63. Exp Cell Res 315(9):1584–1592 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Exosomes · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Exosomes are formed within the endosomal network, a membranous compartment that sorts the various intraluminal vesicles and directs them to their appropriate destinations, including lysosomes and cell surface membranes.”
- Also stated in: § Exosomes · plain
“On the other hand, fusion with the plasma membrane results in the secretion of the 30-100 nm vesicles into the extra-cellular space. These excreted vesicles are exosomes.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Exosomes
What the sources say
- Partly supportedcites [27] Sotelo JR, Porter KR (1959) An electron microscope study of the rat ovum. J Biophys Biochem Cytol 5(2):327–342 sourceExperimental — accuracy not yet measured
Text-fig. 2 (p. 340) depicts multivesicular bodies containing small vesicles and apparently discharging their contents in rat egg cytoplasm. The paper does not identify those vesicles as exosomes or describe endosomal sorting, fusion with the plasma membrane, or secretion of 30–100 nm vesicles. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Exosomes · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TSG101 and Alix are two other proteins sometimes used as exosome markers [38, 46, 47].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Exosomes
What the sources say
- Could not verifycites [38] Kosaka N et al (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285(23):17442–17452 sourceExperimental — accuracy not yet measured
The exosome-characterization passage (Figure 2; page unavailable) identifies CD63 as an exosome marker, not Alix or TSG101. The Alix passages (Figure 5; page unavailable) examine its role in miRNA secretion. Searches for TSG101 and for Alix as an exosome marker found no passage supporting the attributed claim. (LLM, conf=0.78)
- Supportedcites [46] Lasser C, Eldh M, Lotvall J (2012) Isolation and characterization of RNA-containing exosomes. J Vis Exp 59:e3037 source
The Protocol section (“Exosome detection by Western blot”) names Tsg101 and alix among proteins enriched in exosomes and commonly used for exosome detection. The Discussion likewise says their detection helps indicate that a pellet is enriched in exosomes, while noting that no protein marker is absolutely unique to exosomes. (LLM, conf=0.94)
- Supportedcites [47] Fernandez-Llama P et al (2012) Tamm-Horsfall protein and urinary exosome isolation. Kidney Int 77(8):736–742 source
The Results section (‘Electron microscopy’) explicitly calls Alix and TSG101 ‘two exosomal markers’ and reports using immunoblotting to detect them. The Discussion likewise refers to them as exosomal marker proteins. (LLM, conf=0.94)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“CD9 and CD63 serve as the most commonly used identifiers of exosomes and have been targeted for selective isolation [37, 38].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Exosomes
What the sources say
- Partly supportedcites [37] Jansen FH et al (2009) Exosomal secretion of cytoplasmic prostate cancer xenograft-derived proteins. Mol Cell Proteomics 8(6):1192–1205 sourceExperimental — accuracy not yet measured
In “Identification of 44 Tumor-derived Proteins” (page not provided), the paper calls CD9 an established marker of tumor cell-derived exosomes. Its methods and exosome-analysis sections describe purification with anti-CD9 magnetic beads. The cited passages do not establish that CD9 and CD63 are the most commonly used identifiers, or describe CD63-targeted isolation. (LLM, conf=0.87)
- Partly supportedcites [38] Kosaka N et al (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285(23):17442–17452 sourceExperimental — accuracy not yet measured
The exosome-characterization passage (Fig. 2; page unavailable) identifies CD63 as an exosome marker, and its caption reports immunoprecipitating a CD63-positive exosome fraction with an anti-CD63 antibody. Our copy does not identify CD9 as an exosome marker or show its use for selective isolation, and it does not establish that CD9 and CD63 are the most commonly used identifiers. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“CD63 and CD9 are potential markers of exosomes [22, 117]. Markers of microvesicles are less well established though ARF6 and VCAMP3 are recently proposed [66]. TSP and C3b are generally accepted markers of apoptotic bodies. The RLPs are less well studied though Gag protein may be a marker for this group of EVs (Table 1).”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Potential Surface Markers for Defining Clinically Isolated EVs
What the sources say
- Partly supportedcites [22] Escola JM et al (1998) Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 273(32):20121–20127 sourceExperimental — accuracy not yet measured
The citation is attached to the exosome-marker sentence, not the subsequent claims about other vesicle types. The Discussion (page unavailable) reports that CD63 is enriched on exosomes, supporting its use as a potential marker. The copy does not identify CD9 as an exosome marker (searched: CD9). (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [117] Bard MP et al (2004) Proteomic analysis of exosomes isolated from human malignant pleural effusions. Am J Respir Cell Mol Biol 31(1):114–121 source
- Supportedcites [66] Muralidharan-Chari V et al (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19(22):1875–1885 source
The citation is attached to the microvesicle-marker sentence, not the separate claims about exosomes, apoptotic bodies, or RLPs. In the Results section ('Selective sorting of cargo into cell surface microvesicles'; page unavailable), the paper reports that shed microvesicles contain ARF6 and VAMP3, supporting their proposed use as markers. The citing sentence prints 'VCAMP3,' apparently referring to VAMP3. (LLM, conf=0.89)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Membrane budding/vesicle formation is induced by translocation of phosphatidylserine to the outer-membrane leaflet [62, 65]. The budding process is completed through contraction of cytoskeletal structures by actin-myosin interactions [66, 67].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Microvesicles
What the sources say
- Not checked — no full text of the sourcecites [62] Zwaal RF, Schroit AJ (1997) Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 89(4):1121–1132 source
- Not checked — no full text of the sourcecites [65] Hugel B et al (2005) Membrane microparticles: two sides of the coin. Physiology (Bethesda) 20:22–27 source
- Supportedcites [66] Muralidharan-Chari V et al (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19(22):1875–1885 source
The Results section (‘ERK facilitates microvesicle shedding by phosphorylating myosin light chain’) reports that inhibiting myosin II or actin polymerization prevents microvesicle release. The Discussion says actomyosin-based contraction at vesicle necks leads to release, supporting the second sentence, to which this source is cited. The phosphatidylserine claim is cited to other sources. (LLM, conf=0.93)
- Partly supportedcites [67] McConnell RE et al (2009) The enterocyte microvillus is a vesicle-generating organelle. J Cell Biol 185(7):1285–1298 sourceExperimental — accuracy not yet measured
The citation is attached to the sentence about actin–myosin interactions. The Introduction describes myosin-1a moving microvillar membrane over actin bundles and vesicles shedding from the tips, but the Discussion (‘Myo1a is required for proper LV production’; page unavailable) says its precise role in vesicle formation and release remains unclear. It does not establish that cytoskeletal contraction completes budding. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, mRNA profiling of serum derived EV contents can discriminate between healthy and glioblastoma bearing patients [118]. IDH-1 (isocitrate dehydrogenase 1) transcripts have been detected from EVs isolated from the blood of glioblastoma bearing patients using immunoisolations of EVs targeting CD63 [119].”
- Also stated in: § Clinical Applications · plain
“Genetic mutations of mRNA such as EGFRvIII has been detected by nested PCR of EVs isolated from the serum of glioblastoma patients [1], and c-myc amplification has been effectively identified in the serum of medulloblastoma xenograft bearing mice [120].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Clinical Applications
What the sources say
- Supportedcites [118] Noerholm M et al (2012) RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls. BMC Cancer 12(1):22 source
The citation to this paper [118] supports the first sentence, not the subsequent IDH-1 sentence cited to [119]. The Background says serum-microvesicle mRNA expression can differentiate glioblastoma patients from normal controls, and the Results report that RNA expression profiles separated the two groups. The supplied passages do not give page numbers. (LLM, conf=0.93)
- Partly supportedcites [119] Chen C et al (2010) Microfluidic isolation and transcriptome analysis of serum microvesicles. Lab Chip 10(4):505–511 sourceExperimental — accuracy not yet measured
The Results section ('Extraction of RNA from captured microvesicles'; page unavailable) reports less microvesicle RNA in healthy serum than in glioblastoma patient serum. It does not show that mRNA profiles discriminate between the two groups: the two mRNAs tested were detected in both. The IDH-1 statement in the printed sentence carries a different citation and is not attributed to this paper here. (LLM, conf=0.84)
- Partly supportedcites [1] Skog J et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10(12):1470–1476 sourceExperimental — accuracy not yet measured
In the paper’s biomarker results (page not available), EGFRvIII mRNA was detected in serum microvesicles from 7 of 25 glioblastoma patients and in none of 30 normal control sera. That supports a distinction for this specific marker, but not the broader claim that mRNA profiling of serum-derived EVs can discriminate glioblastoma-bearing patients from healthy people generally. The IDH-1 sentence is attached to a different citation and is not assessed here. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Clinical Applications · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Relative to this population, EVs derived from tumors remain a small minority of total EVs isolated in a given biofluid sample [118]. Thus, the sensitivity of detection remains a major challenge in tumor-specific biomarker development.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Clinical Applications
What the sources say
- Partly supportedcites [118] Noerholm M et al (2012) RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls. BMC Cancer 12(1):22 sourceExperimental — accuracy not yet measured
The Discussion says tumour-derived microvesicles in blood are likely to constitute a relatively small fraction of the total in many cases. The citing sentence presents this as categorical and extends it to biofluid samples generally; the cited paper's passage is qualified and concerns blood. The following sentence about detection sensitivity is the citing authors' inference, not a separately cited claim. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: EVs derived from clinical samples are highly heterogeneous in make-up and arise from diverse biologic processes.
- Rests on an assumption: There is no general consensus as to the best method for EV isolation.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For instance, actin-myosin interactions appear critical to the formation of all four types of EVs [66, 85, 100, 115].”
- Also stated in: § Potential Surface Markers for Defining Clinically Isolated EVs · hedged
“As another example, the translocation of phosphatidylserine to the outer membrane appeared a common feature during the formation of both apoptotic bodies and microvesicles [65, 106].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Potential Surface Markers for Defining Clinically Isolated EVs
What the sources say
- Partly supportedcites [66] Muralidharan-Chari V et al (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19(22):1875–1885 sourceExperimental — accuracy not yet measured
The Results section ('ERK facilitates microvesicle shedding by phosphorylating myosin light chain') and Discussion support an actomyosin-dependent mechanism for microvesicle release. They do not establish that actin–myosin interactions are critical to formation of all four EV types. The Results also show phosphatidylserine externalization on microvesicles, but do not establish the stated comparison with apoptotic bodies. (LLM, conf=0.88)
- Partly supportedcites [85] Gladnikoff M et al (2009) Retroviral assembly and budding occur through an actin-driven mechanism. Biophys J 97(9):2419–2428 sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports that actin remodeling helps retroviruses assemble and bud, supporting a limited connection between the cytoskeleton and particle formation. It does not establish that actin–myosin interactions are critical to formation of all four EV types; its myosin discussion describes earlier in vitro work, not a test of EV formation. The phosphatidylserine statement is not part of the supplied citing sentence and is not judged here. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [100] Sebbagh M et al (2001) Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol 3(4):346–352 source
- Not checked — no full text of the sourcecites [115] Piper RC, Katzmann DJ (2007) Biogenesis and function of multivesicular bodies. Annu Rev Cell Dev Biol 23:519–547 source
- Not checked — no full text of the sourcecites [65] Hugel B et al (2005) Membrane microparticles: two sides of the coin. Physiology (Bethesda) 20:22–27 source
- Could not verifycites [106] Martinez MC, Freyssinet JM (2001) Deciphering the plasma membrane hallmarks of apoptotic cells: phosphatidylserine transverse redistribution and calcium entry. BMC Cell Biol 2:20 sourceExperimental — accuracy not yet measured
The citation is attached to the sentence about actin–myosin interactions in the formation of all four EV types. Our copy’s Background and Results discuss calcium entry and phosphatidylserine externalization during apoptosis, but no passage found addresses actin–myosin interactions or formation of four EV types (searched: actin–myosin, actomyosin, myosin, and EV formation). (LLM, conf=0.75)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Potential Surface Markers for Defining Clinically Isolated EVs · hedged
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In a melanoma model, overexpression of a rho family member, GTP-binding protein ADP-ribosylation factor 6 (ARF6), results in increased microvesicle secretion.”
- Also stated in: § Microvesicles · plain
“Interestingly, this signaling cascade does not significantly alter the secretion of vesicles in the size range classically associated with exosomes (50-70 nm vesicles) [66]. These observations provide further support that the biogenesis of microvesicles and exosomes are distinct.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Microvesicles
What the sources say
- Partly supportedcites [66] Muralidharan-Chari V et al (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19(22):1875–1885 sourceExperimental — accuracy not yet measured
The Results section (‘Phenotypic variations of LOXARF6-GDP and LOXARF6-GTP cell lines’; page unavailable) reports significantly increased vesicle shedding from cells expressing active ARF6 compared with parental cells. The Introduction identifies ARF6 as belonging to the ARF family, not the Rho family as the printed citing sentence states. The Results distinguish the isolated microvesicles from exosomes by size and sedimentation, but do not establish the quote’s additional claim that exosome secretion was not significantly altered. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Microvesicles · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The identification of cancer-specific material in EVs isolated from the biofluids (e.g. serum, cerebrospinal fluid, urine) of cancer patients suggests EVs as an attractive platform for biomarker development.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: EVs derived from clinical samples are highly heterogeneous in make-up and arise from diverse biologic processes.
- Rests on an assumption: Multiple types of EV may be present in a given biofluid.
In the paper
“Current isolation methods rely largely on size and density variations of vesicles and/or markers such as CD63 [126] which may or may not be specific to a single type of EV.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Clinical Applications
What the sources say
- Not matchedcites [126]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: There is no general consensus as to the best method for EV isolation.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Each of these populations likely harbor distinct vesicular contents.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Concluding Remarks
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“While tumor specific genetic and proteomic materials have been described in EVs derived from clinical biofluids”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Concluding Remarks
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“In this study, Shao et al. report the fabrication of a microfluidic chip that quantifies presence of glioblastoma specific proteins, including EGFR, EGFRvIII, podoplanin (PDPN), and IDH1 R132H proteins by a micro-nuclear magnetic resonance (μNMR) [122].”
- Also stated in: § Clinical Applications · plain
“This technology allows detection of EV harboring glioblastoma-specific proteins with a sensitivity that is orders of magnitude above existing proteomic methods including, Western blotting and enzyme-linked immunosorbent assays (ELISA).”
- Also stated in: § Clinical Applications · hedged
“Furthermore, changes in EV protein profiles in serial serum sampling of glioblastoma patients appeared to closely track eventual clinical response [122].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Clinical Applications
What the sources say
- Not checked — no full text of the sourcecites [122] Alvarez-Erviti L et al (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29(4):341–345 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Clinical Applications · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, there has not been a careful assessment in terms of the specificity or sensitivity by which these biomarkers define exosomes. It is unlikely that any surface marker will single-handedly define EVs as exosomes.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Exosomes
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Markers for EV types are established using non-neoplastic cell lines.
- Rests on an assumption: The cellular processes leading to formation of the various types of vesicles remain incompletely understood.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Current understanding of EVs suggests that the vesicles are a mixed population of exosomes, microvesicles, RLPs, and apoptotic bodies.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Concluding Remarks
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Whereas exosomes, microvesicles, and RLPs are secreted during normal cellular processes, apoptotic bodies are formed only during programmed cell death.”
- Also stated in: § Apoptotic Bodies · boosted
“Annexin V, thrombospondin, and C3b thus, serve as three well-accepted markers of apoptotic bodies [111].”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Apoptotic Bodies
What the sources say
- Not checked — no full text of the sourcecites [111] van Engeland M et al (1998) Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 31(1):1–9 source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Apoptotic Bodies · boosted
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Retrovirus-like Particles (RLPs) are those that resemble retroviral vesicles on EM but are non-infectious because they do not contain the full complement of genes required for cellular entry or viral propagation. These vesicles are typically defined by their size (90-100 nm) and the presence of a subset of retroviral proteins [69-72].”
- Also stated in: § Retrovirus-Like Particles (RLPs) · plain
“RLPs arise by directly budding from the plasma membrane [83] (Figure 5). However, the mechanism of biogenesis is thought to be distinct from the plasma membrane dynamics related to microvesicle or exosome formation.”
- Also stated in: § Retrovirus-Like Particles (RLPs) · hedged
“As such, the Gag protein may serve a marker for RLPs.”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Retrovirus-Like Particles (RLPs)
What the sources say
- Not checked — no full text of the sourcecites [69] Bronson DL et al (1979) Induction of retrovirus particles in human testicular tumor (Tera-1) cell cultures: an electron microscopic study. J Natl Cancer Inst 63(2):337–339 source
- Not checked — no full text of the sourcecites [70] Boller K et al (1993) Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. Virology 196(1):349–353 source
- Not checked — no full text of the sourcecites [71] Mueller-Lantzsch N et al (1993) Human endogenous retroviral element K10 (HERV-K10) encodes a full-length gag homologous 73-kDa protein and a functional protease. AIDS Res Hum Retroviruses 9(4):343–350 source
- Not checked — no full text of the sourcecites [72] Dewannieux M, Blaise S, Heidmann T (2005) Identification of a functional envelope protein from the HERV-K family of human endogenous retroviruses. J Virol 79(24):15573–15577 source
- Not checked — no full text of the sourcecites [83] Bieda K, Hoffmann A, Boller K (2001) Phenotypic heterogeneity of human endogenous retrovirus particles produced by teratocarcinoma cell lines. J Gen Virol 82(Pt 3):591–596 source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Retrovirus-Like Particles (RLPs) · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the biogenesis and constitution of these vesicles remain poorly understood”
§ Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies > Concluding Remarks
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper relies on this without support.
EVs derived from clinical samples are highly heterogeneous in make-up and arise from diverse biologic processes.
“It is important to recognize that the EV derived from clinical samples are likely highly heterogeneous in make-up and arose from diverse sets of biologic processes.”
The paper relies on this without support.
Multiple types of EV may be present in a given biofluid.
“it is important to recognize and understand that multiple types of EV may be present in a given biofluid.”
The paper relies on this without support.
Markers for EV types are established using non-neoplastic cell lines.
“It is important to recognize that these markers are established using non-neoplastic cell lines.”
The paper relies on this without support.
The cellular processes leading to formation of the various types of vesicles remain incompletely understood.
“the cellular processes leading to the formation of the various types of vesicles remain incompletely understood.”
The paper relies on this without support.
There is no general consensus as to the best method for EV isolation.
“There is no general consensus as to the best method for isolation.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“There are three major categories of EVs, namely exosomes, microvesicles, and apoptotic bodies, which are classified based on their biogenesis mechanism [39, 40].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [39]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In many prior research into EVs, EVs have been conventionally classified into three main categories: exosomes, microvesicles, and apoptotic bodies based on their biogenesis mechanism [39, 40].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [39]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“For instance, vesicles isolated from biofluids using the same methods can be referred to as exosomes by some [9, 10], microvesicles by others [1, 13], and still others blur the difference with the term ‘‘exosomes/microvesicles’’ [14].”
Cited work 10.1016/j.ygyno.2008.04.033 · retracted 2023-07-20 · notice 10.1016/j.ygyno.2023.06.002 · this paper published 2013-03-02
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“These vesicles are secreted by both normal cells and cancerous cells as a means of cell-to-cell communication [2–5].”
Cited work 10.4049/jimmunol.176.3.1534 · retracted 2015-06-15 · notice 10.4049/jimmunol.1500893 · this paper published 2013-03-02
Citations
Cites
2 retracted
RETRACTED: MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer
Taylor, D. D., & Gerçel-Taylor, Ç. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.04.033 · Cited by 2,333 · cited 2×
“For instance, vesicles isolated from biofluids using the same methods can be referred to as exosomes by some [9, 10], microvesicles by others [1, 13], and still others blur the difference with the term ‘‘exosomes/microvesicles’’ [14].”
RetractedPregnancy-Associated Exosomes and Their Modulation of T Cell Signaling
Taylor, D. D., Akyol, S., & Gercel-Taylor, C. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.3.1534 · Cited by 297 · cited 1×
“These vesicles are secreted by both normal cells and cancerous cells as a means of cell-to-cell communication [2–5].”
RetractedApoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673 · cited 2×
“Apoptosis is a major mechanism of cell death for both normal and cancerous cells [93, 94].”
Apoptosis: A Review of Programmed Cell Death
Elmore, S. (2007) · Toxicologic Pathology · doi:10.1080/01926230701320337 · Cited by 13,853 · cited 3×
“During normal development, most apoptotic bodies are phagocytosed by macrophages [94, 97, 101] and are cleared locally.”
Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007) · Nature Cell Biology · doi:10.1038/ncb1596 · Cited by 12,834 · cited 1×
“For instance, vesicles isolated from biofluids using the same methods can be referred to as exosomes by some [9, 10], microvesicles by others [1, 13], and still others blur the difference with the term ‘‘exosomes/microvesicles’’ [14].”
Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids
Théry, C., Amigorena, S., Raposo, G., & Clayton, A. (2006) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb0322s30 · Cited by 5,766 · cited 1×
“Purification by density gradient using sucrose gradients has also been reported [17].”
Exosomes: composition, biogenesis and function
Théry, C., Zitvogel, L., & Amigorena, S. (2002) · Nature reviews. Immunology · doi:10.1038/nri855 · Cited by 5,355 · cited 1×
“Such translocation may also occur during exosome formation [116].”
Skog, J., Würdinger, T., van Rijn, S., Meijer, D. H., Gainche, L., Curry, W. T., Carter, B. S., Krichevsky, A. M., & Breakefield, X. O. (2008) · Nature Cell Biology · doi:10.1038/ncb1800 · Cited by 5,001
Self-citationDelivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930 · cited 1×
“For instance, EVs derived from dendritic cells engineered to express rabies viral glycoprotein have been successfully used to deliver siRNA across the blood brain barrier in murine models providing proof-of-principle of their delivery potential for drugs and genes [122].”
Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes
Trajković, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., Schwille, P., Brügger, B., & Simons, M. (2008) · Science · doi:10.1126/science.1153124 · Cited by 3,760 · cited 2×
“For example, ESCRT independent mechanisms of exosome formation have been reported in some experimental systems [48, 49].”
Research works printed but not linked: 1
- Bronson DL et al (1979) Induction of retrovirus particles in human testicular tumor (Tera-1) cell cultures: an electron microscopic study. J Natl Cancer Inst 63(2):337–339
Cited by
Sorted by citations
Abels, E. R., & Breakefield, X. O. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0366-z · Cited by 1,755
“…been classified based on differences in biogenesis, we will focus on the different molecular mechanisms resulting in either the release of vesicles upon the fusion of the MVBs with the plasma membrane or the release via the outward budding and fission of the plasma membrane (Akers et al. 2013).”
New Technologies for Analysis of Extracellular Vesicles
Shao, H., Im, H., Castro, C. M., Breakefield, X. O., Weissleder, R., & Lee, H. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00534 · Cited by 1,697
Extracellular vesicles as tools and targets in therapy for diseases
Kumar, M. A., Baba, S. K., Sadida, H. Q., Al-Marzooqi, S. K., Jerobin, J., Altemani, F. H., Algehainy, N. A., Alanazi, M. A., Abou‐Samra, A., Kumar, R., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01735-1 · Cited by 1,545
Isolation of Extracellular Vesicles: General Methodologies and Latest Trends
Konoshenko, M. Y., Lekchnov, E. A., Vlassov, A. V., & Laktionov, P. P. (2018) · BioMed Research International · doi:10.1155/2018/8545347 · Cited by 1,302
“Apoptotic bodies carry fragmented genomic DNA and cell organelles, which distinguishes them from the other EV types [13, 15, 22].”
BackgroundMesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications
Rani, S., Ryan, A. E., Griffin, M. D., & Ritter, T. (2015) · Molecular Therapy · doi:10.1038/mt.2015.44 · Cited by 1,251
Effect of exosomal miRNA on cancer biology and clinical applications
Sun, Z., Shi, K., Yang, S., Liu, J., Zhou, Q., Wang, G., Song, J., Li, Z., Zhang, Z., & Yuan, W. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0897-7 · Cited by 800
“Cancer cells secrete at least 10-fold more exosomes than do normal cells, and tumor-derived exosomes (TDEs) can facilitate cell-cell communication through the transport of growth factors, chemokines, microRNAs, and other small molecules [4, 5].”
BackgroundExosomes: Large-scale production, isolation, drug loading efficiency, and biodistribution and uptake
Kimiz-Gebologlu, I., & Oncel, S. S. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.05.027 · Cited by 722
Emerging role of extracellular vesicles in inflammatory diseases
Buzás, E. I., György, B., Nagy, G., Falus, A., & Gay, S. (2014) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2014.19 · Cited by 684
Extracellular Vesicles Isolated from the Leaf Apoplast Carry Stress-Response Proteins
Rutter, B. D., & Innes, R. W. (2016) · PLANT PHYSIOLOGY · doi:10.1104/pp.16.01253 · Cited by 663
“…while exosomes are released from a cell after the fusion of a multivesicular body (MVB) with the PM (György et al., 2011; van der Pol et al., 2012; Akers et al., 2013) Exosomes were originally thought to function as a waste disposal system, but more recent findings indicate that they mediate…”
ResultPatel, G. K., Khan, M. A., Zubair, H., Srivastava, S. K., Khushman, M. M., Singh, S., & Singh, A. P. (2019) · Scientific Reports · doi:10.1038/s41598-019-41800-2 · Cited by 657
Exosome Processing and Characterization Approaches for Research and Technology Development
Lai, J. J., Chau, Z. L., Chen, S., Hill, J. J., Korpany, K. V., Liang, N., Lin, L., Lin, Y., Liu, J. K., Liu, Y., et al. (2022) · Advanced Science · doi:10.1002/advs.202103222 · Cited by 623
Lai, C. P., Kim, E. Y., Badr, C. E., Weissleder, R., Mempel, T. R., Tannous, B. A., & Breakefield, X. O. (2015) · Nature Communications · doi:10.1038/ncomms8029 · Cited by 574
Virus budding and the ESCRT pathway
Votteler, J., & Sundquist, W. I. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.08.012 · Cited by 547
“Moreover, even in uninfected cells, vesicles can bud directly from the plasma membrane (termed shedding microvesicles or ectosomes) (Akers et al., 2013; Nabhan et al., 2012).”
BackgroundApoptotic Cell-Derived Extracellular Vesicles: More Than Just Debris
Caruso, S., & Poon, I. K. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01486 · Cited by 541
“Arthritis Rheum (2002) 46(1): 191–201.”
BackgroundInfluentialHe, M., Crow, J., Roth, M., Zeng, Y., & Godwin, A. K. (2014) · Lab on a Chip · doi:10.1039/c4lc00662c · Cited by 512
Extracellular vesicles as drug delivery systems: Lessons from the liposome field
van der Meel, R., Fens, M. H. A. M., Vader, P., van Solinge, W. W., Eniola‐Adefeso, O., & Schiffelers, R. M. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.07.049 · Cited by 498
Apoptotic Bodies: Particular Extracellular Vesicles Involved in Intercellular Communication
Battistelli, M., & Falcieri, E. (2020) · Biology · doi:10.3390/biology9010021 · Cited by 507
“The apoptotic cell disassembly process and the apoptotic material removal by phagocytes are very rapid, therefore the presence of apoptotic bodies (ApoBDs) is very limited in vivo [23], (Figure 2).”
BackgroundGetting to the Outer Leaflet: Physiology of Phosphatidylserine Exposure at the Plasma Membrane
Bevers, E. M., & Williamson, P. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00020.2015 · Cited by 457
“PS-exposing microvesicles could be observed in the extracellular space between apoptotic cells and surrounding phagocytes, suggesting that vesicles shed from apoptotic cells (2) might support a net transfer of PS from target to phagocyte (169) or even accumulation of vesicles captured by tethering receptors (186).”
BackgroundVascular Calcification—New Insights into Its Mechanism
Lee, S., Lee, I. K., & Jeon, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082685 · Cited by 451
“Based on their mechanism of biogenesis, extracellular vesicles are classified into three types: exosomes, microvesicles and apoptotic bodies [90].”
BackgroundChallenges in Exosome Isolation and Analysis in Health and Disease
Ludwig, N., Whiteside, T. L., & Reichert, T. E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194684 · Cited by 430
“Due to the endosomal origin, exosomes are enriched in late endosome components such as CD63, CD9 and CD81 [3].”
BackgroundExosomes: new molecular targets of diseases
Samanta, S., Rajasingh, S., Drosos, N., Zhou, Z., Dawn, B., & Rajasingh, J. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.162 · Cited by 437
Extracellular vesicles as biomarkers and therapeutic targets for cancer
Urabe, F., Kosaka, N., Ito, K., Kimura, T., Egawa, S., & Ochiya, T. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00280.2019 · Cited by 413
RNA-binding proteins contribute to small RNA loading in plant extracellular vesicles
He, B., Cai, Q., Qiao, L., Huang, C., Wang, S., Miao, W., Ha, T., Wang, Y., & Jin, H. (2021) · Nature Plants · doi:10.1038/s41477-021-00863-8 · Cited by 400
Challenges in the development and establishment of exosome-based drug delivery systems
Wang, J., Chen, D., & Ho, E. A. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.10.020 · Cited by 391
Exosome Biogenesis, Regulation, and Function in Viral Infection
Alenquer, M., & Amorim, M. J. (2015) · Viruses · doi:10.3390/v7092862 · Cited by 373
“In recent years, a plethora of reports and reviews has explored several functions of exosomes in mediating intercellular communication, immune system functions, development and differentiation, neuronal function, cell signaling, regeneration [1,14–21], and several steps in viral replication, the latter topic explored…”
BackgroundLong Noncoding RNAs as Biomarkers in Cancer
Bolha, L., Ravnik‐Glavač, M., & Glavač, D. (2017) · Disease Markers · doi:10.1155/2017/7243968 · Cited by 367
“Among the main advantages of lncRNAs that make them suitable as cancer diagnostic and prognostic biomarkers is their high stability while circulating in body fluids, especially when included in exosomes or apoptotic bodies [72].”
BackgroundApoptotic cell-derived exosomes: messages from dying cells
Kakarla, R., Hur, J., Kim, Y. J., Kim, J., & Chwae, Y. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0362-8 · Cited by 369
Balusu, S., Wonterghem, E. V., Rycke, R. M. D., Raemdonck, K., Stremersch, S., Gevaert, K., Brkić, M., Demeestere, D., Vanhooren, V., Hendrix, A., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606271 · Cited by 350
“TEM analysis revealed that the CSF contained EVs of ~100 nm, which are known to contain miRNA and to be important mediators of cell–cell communication (Akers et al, 2013; El Andaloussi et al, 2013; Raposo & Stoorvogel, 2013; Colombo et al, 2014; Yanez-Mo et al, 2015).”
BackgroundConcise Review: Developing Best-Practice Models for the Therapeutic Use of Extracellular Vesicles
Reiner, A. T., Witwer, K. W., van Balkom, B. W. M., de Beer, J., Brodie, C., Corteling, R. L., Gabrielsson, S., Gimona, M., Ibrahim, A., de Kleijn, D. P. V., et al. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0055 · Cited by 356
Akers, J. C., Ramakrishnan, V., Kim, R., Skog, J., Nakano, I., Pingle, S. C., Kalinina, J., Hua, W., Kesari, S., Mao, Y. Q., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078115 · Cited by 347
“EVs isolated from biofluids can encompass exosomes, microvesicles, retrovirus-like particles (RLPs) and apoptotic bodies [66,67].”
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“purposes, meanwhile, apoptotic bodies are larger structures (500-4000 nm) formed during apoptosis for the disintegration of the cellular content.(1) On their part, exosomes are a particular subpopulation of EVs secreted by most cell types through the endocytic pathway.”
BackgroundThe Exosome ‐ A Naturally Secreted Nanoparticle and its Application to Wound Healing
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Mast cell‐neural interactions contribute to pain and itch
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The emerging role of extracellular vesicles as biomarkers for urogenital cancers
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“Extracellular vesicles (EVs) are particles produced by various cells, ranging from microbial and plant to human cells [1].”
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“The three major categories of EVs are (a) apoptotic bodies, (b) microparticles or microvesicles, and (c) exosomes or nanovesicles [24].”
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“In terms of identifying apoptotic bodies, thrombospondin and complement component C3b are in many cases accepted apoptotic body markers.(1) Unlike the 2 other vesicle types, apoptotic bodies are distinguished by containing organelles, DNA fragments, and histones as a part of the vesicular cargo in addition to proteins…”
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“The ABs are released from the outward protrusion of the plasma membrane during the late phase of cell death by apoptosis and are featured by the presence of organelles inside the vesicles (85,86).”
BackgroundExosome in Tumour Microenvironment: Overview of the Crosstalk between Normal and Cancer Cells
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“Microparticles form by outward budding of the plasma membrane, while exosomes are secreted by plasma membrane fusion with multi-vesicular bodies (MVBs) that form by invagination of late endosomal membranes into intraluminal vesicles (ILVs) (Akers et al., 2013).”
BackgroundAdvances in Drug Delivery Systems Based on Red Blood Cells and Their Membrane-Derived Nanoparticles
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“Importantly, the reproducibility of EVs strongly depends on cell living environments (such as physiological or pathological conditions) [56], and complex subpopulations of EVs are inevitably distinguished and separated because three types of EVs (exosomes, microvesicles and apoptotic bodies) are similar in structure a…”
Extracellular Vesicles in Human Reproduction in Health and Disease
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“of phosphatidylserine to the outer-membrane leaflet through the activity of aminophospholipid translocases (29).”
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“Apoptotic bodies have the widest spread diameter, which can range from approximately 50–5000 nm [113].”
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“A notable distinction between apoptotic bodies and the other two major EV groups is that apoptotic bodies also contain fragmented DNA and cell organelles from their host cell [15, 16].”
BackgroundTissue‐derived extracellular vesicles in cancers and non‐cancer diseases: Present and future
Li, S.-R., Man, Q., Gao, X., Lin, H., Wang, J., Su, F., Wang, H., Bu, L., Liu, B., & Chen, G. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12175 · Cited by 206
“ABs are released from cells undergoing programmed cell death through outward blebbing and fragmentation of the PM (Akers et al., 2013), with a broad size range of 100–5000 nm in diameter (Mathieu et al.”
BackgroundInfluentialExosomes: Decreased Sensitivity of Lung Cancer A549 Cells to Cisplatin
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“Fusion of the MVE with the plasma membrane leads to the release of the internal vesicles known as exosomes [11].”
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“In addition, studies evaluating GB-derived EVs in CSF indicated that elevated miR-21 levels are associated with worse prognosis (Akers et al., 2013; Shi et al., 2015).”
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TRAIL delivery by MSC‐derived extracellular vesicles is an effective anticancer therapy
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“in diameter, and contain marker proteins such as tetraspanins CD9, CD63 and CD81, flotillin, ALG2-interacting protein X (ALIX) and tumour susceptibility gene 101 protein [8,10,11].”
BackgroundEffective methods for isolation and purification of extracellular vesicles from plants
Huang, Y., Wang, S., Cai, Q., & Jin, H. (2021) · Journal of Integrative Plant Biology · doi:10.1111/jipb.13181 · Cited by 199
“For example, exosomes, microvesicles and apoptotic bodies each represent a major class of EVs, and originate from multivesicular bodies (MVBs), the plasma membrane, or apoptotic cells during apoptosis, respectively (Akers et al., 2013; Colombo et al., 2014; van Niel et al., 2018).”
BackgroundSnoderly, H. T., Boone, B. A., & Bennewitz, M. F. (2019) · Breast Cancer Research · doi:10.1186/s13058-019-1237-6 · Cited by 195
Extracellular Vesicles and Exosomes: Insights From Exercise Science
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“Over the last two decades, there has been an accelerated interest in exosome research because of their putative role as mediators of intercellular communication, with relevance to pathophysiology, diagnostics, drug delivery, and discovery of new therapeutic compounds (Akers et al., 2013; Lässer, 2015; Edgar, 2016).”
BackgroundCai, Q., He, B., Weiberg, A., Buck, A. H., & Jin, H. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1008090 · Cited by 185
“While exosomes and microvesicles are secreted during normal cellular processes, apoptotic bodies are formed during programmed cell death [33].”
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“They are vesicles of information and material from dying cells and were previously regarded as apoptotic debris until they were found to be able to deliver useful material to healthy recipient cells [97].”
BackgroundThe Role of Extracellular Vesicles in Viral Infection and Transmission
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“Size overlap complicates exosome definition due to the presence of other membranederived subcellular structures, such as apoptotic vesicles, exosome-like vesicles, membrane particles, and ectosomes.(27,28) Current exosome purification methods, including ultrafiltration and sucrose gradient ultracentrifugation, are ted…”
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Extracellular vesicles as modulators of wound healing
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Exosomes in Inflammation and Inflammatory Disease
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Cardiac Extracellular Vesicles in Normal and Infarcted Heart
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“EVs carry a variety of molecules, including low molecular compounds, lipids, proteins and genetic material, such as DNA, mRNA and non-coding RNA.”
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“Biogenesis of Apoptotic Bodies Apoptotic bodies are a class of EVs with various sizes between 1000 and 5000 nm, formed exclusively during programmed cell death.(137) Morphological changes such as membrane blebbing, membrane protrusion, and release of apoptotic bodies are characteristic features of apoptotic cells unde…”
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“The biogenesis mechanism distinguishes exosomes, microvesicles, and apoptotic bodies [17].”
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“Since the regulatory mechanisms of EV biogenesis and uptake have been discussed in detail previously (17, 48-50), this review focuses on cargo sorting in EVs, particularly in”
miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients
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“While defining EVs based on the mechanism of biogenesis is attractive [23, 24], such a classification scheme cannot be easily applied to clinical biofluids.”
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“of EVs, their detection, isolation and characterisation from different bodily fluids are currently not optimal or standardised due to their small size and low refractive index (RI) [6, 7, 8, 9, 10].”
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“On the other hand, MVs production can be significantly elevated under various stressor stimulations, including increased concentration of Ca2+, cellular stress and immune system response (Akers et al., 2013), events that can be caused by SOD1, TDP-43, and FUS aggregation in ALS.”
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“MVs are ~200 to ~1000 nm EVs formed by budding of the cell membrane, and apoptotic bodies (500–2000 nm) are products of apoptotic cell disassembly [46,47].”
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“34 Several proteins have been shown to have a role but it is unclear whether their role is cell type-speci fi c. ARF6 has been shown to have an important role in the cargo selection and formation of MVs in melanoma cells.”
Metadata
- Authors
- Akers, J. C., Gonda, D., Kim, R., Carter, B. S., & Chen, C. C.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Chen, Clark C.
- Venue
- Journal of Neuro-Oncology
- Published
- 2013-03-02
- Volume
- 113
- Issue
- 1
- Pages
- 1-11
- ISSN
- 0167-594X (ISSN-L)
- 1573-7373
- PMC
- PMC5533094
- OpenAlex
- W1990597414
- Cited by
- 1,423
- References
- 125
- Citations by year
- 2026: 74 · 2025: 126 · 2024: 138 · 2023: 153 · 2022: 164 · 2021: 179 · 2020: 135 · 2019: 120 · 2018: 93 · 2017: 72 · 2016: 71 · 2015: 48 · 2014: 39 · 2013: 9
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UH2TR000931, UH3TR000931)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- extracellular vesicles, exosomes, microvesicles, apoptotic bodies, vesicle biogenesis, tumor markers, biological fluids, neuro-oncology, tumor-derived extracellular vesicles
- MeSH terms
- Humans, Retroviridae, Biomarkers, Apoptosis, Exosomes
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