Human bone marrow contains high levels of extracellular vesicles with a tissue-specific subtype distribution

Rank, Andreas; Nieuwland, Rienk; Köhler, Anton; Franz, Claudia; Waidhauser, Johanna; Tóth, Bettina

doi:10.1371/journal.pone.0207950

Cited by 4 publications

(4 citation statements)

References 45 publications

(43 reference statements)

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“…Well‐characterized cell‐type‐specific plasma membrane proteins that have been used for EV characterization were used. These include clusters of differentiation (CD) 61 for platelet‐derived EVs (CD61‐allophycocyanin [APC], clone 2C9.G2; Miltenyi Biotec), Mac‐2 (also known as galectin‐3) for macrophage‐derived EVs (Alexa Fluor 448 Galectin‐3; BD Biosciences), RB6‐8C5 antigen for neutrophil‐derived EVs (APC‐Cy7‐lymphocyte antigen 6 complex, locus G/C1 [Ly‐6G and Ly‐6C]; BD Biosciences), and asialoglycoprotein receptor 1 (Asgr1; Proteintech) and cytochrome p450 family 2, subfamily e, polypeptide 1 (Cyp2E1; CYP450‐GP) for hepatocyte‐derived EVs …”

Section: Methodsmentioning

confidence: 99%

Characterization of Cellular Sources and Circulating Levels of Extracellular Vesicles in a Dietary Murine Model of Nonalcoholic Steatohepatitis

Li¹,

Liu

Mauer³

et al. 2019

Hepatol Commun

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Circulating extracellular vesicles (EVs) are a novel and emerging biomarker for nonalcoholic steatohepatitis (NASH). It has been demonstrated that total circulating EVs and hepatocyte‐derived EVs are elevated in male mice with diet‐induced NASH. How hepatocyte‐derived EVs change over time and other cellular sources of EVs in NASH have not been determined. Our objective was to define the quantitative evolution of hepatocyte‐derived, macrophage‐derived, neutrophil‐derived, and platelet‐derived EVs in male and female mice with dietary NASH. Fluorescently labeled antibodies and a nanoscale flow cytometer were used to detect plasma levels of EVs. Asialoglycoprotein receptor 1 (ASGR1) and cytochrome P450 family 2 subfamily E member 1 (CYP2E1) are markers of hepatocyte‐derived EVs; galectin 3 is a marker of macrophage‐derived EVs; common epitope on lymphocyte antigen 6 complex, locus G/C1 (Ly‐6G and Ly‐6C) is a marker of neutrophil‐derived EVs; and clusters of differentiation 61 (CD61) is a marker of platelet‐derived EVs. Nonalcoholic fatty liver disease activity score (NAS) was calculated using hematoxylin and eosin‐stained liver sections, and magnetic resonance imaging (MRI) was used for measurement of the fat fraction and elastography. Hepatocyte‐derived EVs increased in both male and female mice at 12 and 10 weeks of feeding, respectively, and remained elevated at 24 weeks in both male and female mice and at 48 weeks in male mice and 36 weeks in female mice. Macrophage‐ and neutrophil‐derived EVs were significantly elevated at 24 weeks of dietary feeding concomitant with the histologic presence of inflammatory foci in the liver. In fat‐, fructose‐, and cholesterol‐ (FFC) fed male mice, platelet‐derived EVs were elevated at 12, 24, and 48 weeks, whereas in female mice, platelet derived EVs were significantly elevated at 24 weeks. Hepatocyte‐, macrophage‐ and neutrophil‐derived EVs correlated well with the histologic NAS. Conclusion: Circulating cell‐type‐specific EVs may be a novel biomarker for NASH diagnosis and longitudinal follow up.

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Section: Methodsmentioning

confidence: 99%

Characterization of Cellular Sources and Circulating Levels of Extracellular Vesicles in a Dietary Murine Model of Nonalcoholic Steatohepatitis

Li¹,

Liu

Mauer³

et al. 2019

Hepatol Commun

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“…Moreover, bone marrow contains the procoagulant factor tissue thromboplastin, making the risk for thrombosis in surgeries that involve bone higher (Gleeson et al, 2015; Kakkar et al, 2000; Rank et al, 2018). Our heparin group had a slightly higher fraction of FTT that included the osseous component, Even though the increased proportion of FFT that included bone in the UFH compared to the enoxaparin group failed to reach statistical significance, this may have contributed to the higher rate of VTE in the heparin group.…”

Section: Discussionmentioning

confidence: 99%

Association between venous thromboembolism rates and different prophylactic anticoagulation regimens in patients undergoing free flap reconstruction of the head and neck region

et al. 2023

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BackgroundVenous Thromboembolism (VTE) is a serious complication after free tissue transfer to the head and neck (H&N). However, an optimal antithrombotic prophylaxis protocol is not defined in the literature. Enoxaparin 30 mg twice daily (BID) and heparin 5000 IU three times daily (TID) are among the most commonly used regimens for chemoprophylaxis. However, no studies compare these two agents in the H&N population.MethodsA cohort study of patients who underwent free tissue transfer to H&N from 2012 to 2021 and received either enoxaparin 30 mg BID or Heparin 5000 IU TID postoperatively. Postoperative VTE and hematoma events were recorded within 30 days of index surgery. The cohort was divided into two groups based on chemoprophylaxis. VTE and hematoma rates were compared between the groups.ResultsOut of 895 patients, 737 met the inclusion criteria. The mean age and Caprini score were 60.6 [SD 12.5] years and 6.5 [SD 1.7], respectively. 234 [31.88%] were female. VTE and hematoma rates among all patients were 4.47% and 5.56%, respectively. The mean Caprini score between the enoxaparin (n = 664) and heparin (n = 73) groups was not statistically significant (6.5 ± 1.7 vs.6.3 ± 1.3, p = 0.457). The VTE rate in the enoxaparin group was significantly lower than in the heparin group (3.9% vs. 9.6%; OR: 2.602, 95% CI: 1.087–6.225). Hematoma rates were similar between the two groups (5.5% vs. 5.6%; OR: 0.982, 95% CI: 0.339–2.838).ConclusionsEnoxaparin 30 mg BID was associated with a lower VTE rate while maintaining a similar hematoma rate compared to heparin 5000 units TID. This association may support the use of enoxaparin over heparin for VTE chemoprophylaxis in H&N reconstruction.

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“…Especially, are EVs with a high expression of PD-L1 potential biomarkers for the diagnosis or prognosis of MPN, similar to what has been demonstrated with circulating exosomal-PD-L1 in lung cancer, breast cancer [ 146 ], melanoma [ 147 , 148 ], and head and neck cancer [ 149 , 150 ]? So far, the presence of PD-L1 in EVs [ 151 ] and their existence in hematologic malignancies and MPN has not been proved [ 152 ], but there is evidence that large amounts of EVs can be found in the bone marrow compartment [ 153 ].…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Proteins and PD-1/PD-L1 as Potential Therapeutic Targets in Myeloproliferative Neoplasms

Almeida

Regimbeau

Jego

et al. 2020

Cancers

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Myeloproliferative neoplasms (MPN) are a group of clonal disorders that affect hematopoietic stem/progenitor cells. These disorders are often caused by oncogenic driver mutations associated with persistent Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling. While JAK inhibitors, such as ruxolitinib, reduce MPN-related symptoms in myelofibrosis, they do not influence the underlying cause of the disease and are not curative. Due to these limitations, there is a need for alternative therapeutic strategies and targets. Heat shock proteins (HSPs) are cytoprotective stress-response chaperones involved in protein homeostasis and in many critical pathways, including inflammation. Over the last decade, several research teams have unraveled the mechanistic connection between STAT signaling and several HSPs, showing that HSPs are potential therapeutic targets for MPN. These HSPs include HSP70, HSP90 (chaperoning JAK2) and both HSP110 and HSP27, which are key factors modulating STAT3 phosphorylation status. Like the HSPs, the PD-1/PD-L1 signaling pathway has been widely studied in cancer, but the importance of PD-L1-mediated immune escape in MPN was only recently reported. In this review, we summarize the role of HSPs and PD-1/PD-L1 signaling, the modalities of their experimental blockade, and the effect in MPN. Finally, we discuss the potential of these emerging targeted approaches in MPN therapy.

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Human bone marrow contains high levels of extracellular vesicles with a tissue-specific subtype distribution

Cited by 4 publications

References 45 publications

Characterization of Cellular Sources and Circulating Levels of Extracellular Vesicles in a Dietary Murine Model of Nonalcoholic Steatohepatitis

Characterization of Cellular Sources and Circulating Levels of Extracellular Vesicles in a Dietary Murine Model of Nonalcoholic Steatohepatitis

Association between venous thromboembolism rates and different prophylactic anticoagulation regimens in patients undergoing free flap reconstruction of the head and neck region

Heat Shock Proteins and PD-1/PD-L1 as Potential Therapeutic Targets in Myeloproliferative Neoplasms

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