Platelet-derived Microparticles Research Articles

Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets.

The immunosuppressive microenvironment of solid tumours reduces the antitumour activity of chimeric antigen receptor T cells (CAR-T cells). Here, we show that the release-through the implantation of a hyaluronic acid hydrogel-of CAR-T cells targeting the human chondroitin sulfate proteoglycan 4, polymer nanoparticles encapsulating the cytokine interleukin-15 and platelets conjugated with the checkpoint inhibitor programmed death-ligand 1 into the tumour cavity of mice with a resected subcutaneous melanoma tumour inhibits the local recurrence of the tumour as well as the growth of distant tumours, through the abscopal effect. The hydrogel, which functions as a reservoir, facilitates the enhanced distribution of the CAR-T cells within the surgical bed, and the inflammatory microenvironment triggers platelet activation and the subsequent release of platelet-derived microparticles. The post-surgery local delivery of combination immunotherapy through a biocompatible hydrogel reservoir could represent a translational route for preventing the recurrence of cancers with resectable tumours.

To Bleed or Not to Bleed: MCS-Related Shear Stress Promotes Redistribution of GPIb and αIIbβ3 from Platelets to Microparticles Thus Impairing Platelet Hemostatic Function

Purpose Bleeding is a leading cause of readmission and 1-year mortality for mechanical circulatory support (MCS) patients. Mechanical damage of platelets and coagulation proteins induced by MCS-generated high shear stress is the main driver of bleeding. We previously demonstrated that hypershear promotes platelet pro-apoptotic behavior resulting in membrane reorganization and generation of platelet-derived microparticles (PDMP). Here, we test the hypothesis that hypershear alters surface expression and shedding of adhesion receptors GPIb and αIIbβ3 from platelets and PDMPs thus affecting platelet aggregability - all potential bleeding contributors. Methods Human platelets were exposed to shear stress in a hemodynamic shearing device (30-70 dyn/cm2, 10 min). Integrin GPIb and αIIbβ3 surface expression and PDMP generation were quantified by flow cytometry. Single platelets and PDMPs were distinguished by FS/SS characteristics. Shedding of soluble GPIb and αIIbβ3 fragments was quantified by ELISA. Platelet aggregation was measured by optical aggregometry. Results Platelet exposure to hypershear led to a reduction of platelet GPIb surface expression, with a significant drop of GPIb+ platelet number and fluorescence (73.5 ± 2.9% and 953.1 ± 101.0 AU vs. 94.3 ± 0.7% and 1620 ± 72.4 AU for intact platelets; M ± SEM, ANOVA, p ≤ 0.05). Yet, no shear-mediated shedding of soluble GPIb fragment or β3 subunit was found. Downregulation of platelet GPIb expression coincided with a progressive increase of GPIb- & αIIbβ3-positive PDMPs after shear (up to 3.3 ± 0.6% & 12.5 ± 2.8%, correspondingly). Surface density of GPIb and αIIbβ3 on PDMPs was 2-4x higher than on platelets, post-shear. Platelet aggregation to increasing concentrations of ADP and TRAP-6 was significantly impaired by 70 dyn/cm2 shear stress. Conclusion MCS-mediated hypershear and platelet stress accumulation 1) induces downregulation of platelet adhesion receptors via ejection of receptor-enriched PDMPs; 2) does not induce shedding of soluble fragments of GPIb and β3, and; 3) mechanistically limits platelet aggregatory and hemostatic responses. Shear-mediated redistribution of primary adhesion receptors from platelets to PDMPs coupled with impaired aggregability may mechanistically contribute to MCS-related bleeding.

Cell-Derived Microparticles in Blood Products from Blood Donors Deficient in Glucose-6-Phosphate Dehydrogenase.

To quantitate the microparticles (MPs) in whole blood and blood products obtained from blood donors who are deficient in glucose-6-phosphate dehydrogenase (G6PD). The current study analyzed whole blood and blood components prepared from 49 blood donors with G6PD deficiencies and 98 with G6PD-normal results. Packed red blood cells (PRBCs), platelet concentrate (PC), and plasma were prepared according to transfusion laboratory procedures. MP concentrations were determined using a flow cytometer. Blood components prepared from donors with G6PD deficiency were characterized by higher red blood cell-derived MP (RMP) concentration in PRBCs (25,526 vs 18,738 particles/µL) but lower concentrations of platelet-derived MPs (PMPs; in whole blood and PC), leukocyte-derived MPs (LMP; in whole blood and plasma) and total MP (in PC), compared with those from donors with G6PD-normal test results. These results suggest that differences in G6PD status may account for variation in RMP levels during processing.

Early Detection of Negative Smoking Impacts: Vascular Adaptation Deviation Based on Quantification of Circulated Endothelial Activation Markers.

IntroductionSmoking can cause vascular damage in the form of an inflammatory reaction characterized by endothelial activation. Endothelial activation forms a pathological adaptation pattern so that it can induce the atherogenesis process. Several markers, such as E-selectin, platelet-derived micro particles (PMPs) and hematopoietic stem cell (HSC) can identify the activation of endothelial in circulating blood. Therefore, the deviation of vascular adaptation due to smoking can be detected early through the feedback mechanism between E-selectin, PMPs, and HSC.PurposeThis study aims to analyze the initial picture of the negative impact of smoking on vascular adaptation by measuring E-selectin, PMPs, and HSC in the peripheral blood circulation. Participant criteria and methods: Peripheral blood samples (5 mL) were taken from each participant, both the smoking group (n = 30) and the non-smoker group (n = 31) to obtain peripheral blood mononuclear cells (PBMNC). PBMNC was isolated using ficoll-based gradient centrifugation. The flow cytometry assay method used to measure the E-selectin, PMPs and hematopoietic stem cells.ResultsThe mean of circulating E-selectin in smokers was higher than that of non-smokers. On the other hand, the average number of PMPs and HSCs in smokers was lower than non-smokers.ConclusionSmoking increases the risk of accelerated vascular block formation, as indicated by an increase in the amount of circulating E-selectin. The increase in E-selectin in the blood vessels mediates the increased adhesion of PMPs in the vascular area so that the number of circulating PMPs in smokers decreases. The decrease in circulating PMPs decreases the signal of vascular repair, which is characterized by a decline in the number of HSCs.

Plasmatic and cell-based enhancement by microparticles originated from platelets and endothelial cells under simulated in vitro conditions of a dilutional coagulopathy

BackgroundAggressive fluid management and other external factors may lead to hypothermia, acidosis and hemodilution (defined as Lethal Triad, LT) contributing to a trauma-induced coagulopathy (TIC) that worsens patients’ outcomes. Procoagulant microparticles (MP) are crucial players at the interface of cellular and plasmatic coagulation. However, their functions remain largely unexplored. This study aimed to characterize effects of MP subtypes and concentrations on functional coagulation under in vitro simulated conditions.MethodsBlood from eleven volunteers were collected to simulate in vitro conditions of hemodilution (HD) and LT, respectively. HD was induced by replacing a blood volume of 33% by crystalloids and for LT, samples were further processed by reducing the temperature to 32 °C and lowering the pH to 6.8. MP were obtained either from platelet concentrates (platelet-derived MP, PDMP) or from cell culture (ECV304 cells for endothelial-derived MP, EDMP) by targeted stimulation. After introducing MP to in vitro conditions, we measured their concentration-dependent effects (1.000, 10.000 and 15.000 MP/μl blood) on coagulation compared to whole blood (WB). For each condition, coagulation was characterized by flow cytometric platelet activation and by quantification of fibrin clot propagation using Thrombodynamics® technology.ResultsMP originated from platelets and endothelial cells affected blood coagulation in a concentration-dependent manner. Particularly, high PDMP quantities (10.000 and 15.000 PDMP/μl blood) significantly induced platelet activation and fibrin clot growth and size in HD conditions. In LT conditions as well, only high PDMP concentration induced platelet activation, clot growth and size. In contrast, EDMP did not induce platelet activation, but resulted in enhanced formation of spontaneous clots, irrespective of simulated condition. With increasing EDMP concentration, the time until the onset of spontaneous clotting decreased in both HD and LT conditions.DiscussionThe study demonstrates an essential role of MP within the coagulation process under simulated coagulopathic conditions. PDMP affected platelets promoting clot formation likely by providing a surface enlargement. EDMP presumably affected clotting factors of the plasmatic coagulation resulting in an increased formation of spontaneous clots.ConclusionUnder simulated conditions of a dilutional coagulopathy, MP from different cellular origin indicate a divergent but both procoagulant mechanism within the coagulation process.

Platelet Dysfunction During Mechanical Circulatory Support: Elevated Shear Stress Promotes Downregulation of αIIbβ3 and GPIb via Microparticle Shedding Decreasing Platelet Aggregability.

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Exercise and Circulating Microparticles in Healthy Subjects.

This study aimed to explore the relationship between exercise and circulating microparticles (CMPs). PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until August 13, 2020, using the terms "exercise" and "cell-derived microparticles." The Cochrane tool of risk of bias and the Methodological Index for Non-Randomized Studies were used to grade the studies. Twenty-six studies that met criteria were included in this review, including one before-after self-control study, 2 cohort studies, 4 randomized control trials, 5 case-control studies, and 14 descriptive studies. The studies were divided into a single bout and long-term exercise. The types of MPs contained endothelium-derived microparticles (EMPs), leukocyte-derived microparticles (LMPs), platelet-derived microparticles (PMPs), and erythrocyte-derived microparticles (ErMPs). This first systematic review found that the levels of CMPs continued to increase after a single bout of exercise in untrained subjects and were lower in trained subjects. PMPs expressed a transient increase after a single bout of exercise, and the proportion and duration of PMPs increment reduced in long-term exercise. Most studies showed a decline in LMPs in trained subjects after a single bout and long-term exercise, and variable changes were found in EMPs and ErMPs after exercise. A single bout of exercise drives the vessels exposed to high shear stress that promotes the formation of CMPs. However, the decline in CMPs in trained subjects may be attributed to the fact that they have a better ability to adapt to changes in hemodynamics and cellular function during exercise.

Prediction of the Therapeutic Effects of Pembrolizumab and Nivolumab in Advanced Non-Small Cell Lung Cancer by Platelet-Derived Microparticles in Circulating Blood.

Background:There are limited methods to predict the therapeutic effect of immune checkpoint inhibitors (ICIs). The purpose of this study was to explore the value of circulating microparticles (MPs) in predicting thetherapeutic effects of immunotherapy.Methods:A prospective study was conducted at the cancer center of PLA general hospital, including all patients with advanced non-small cell lung cancer (NSCLC) who were treated with pembrolizumab or nivolumab from December 2018 to December 2019. The patients were divided into an immune-related objective response (iOR) group and an immune-related disease progression (iPD) group.The numbers of total MPs, platelet-derived microparticles (PMPs) and T-lymphocyte-derived microparticles (T-LyMPs) at baseline and after immunotherapy were detected using a flow cytometer. Univariate analysis and multivariate logistic regression analysis were used to determine the independent influencing factors.Results:We identified 32 patients in the iOR group and 18 patients in the iPD group. No significant difference were found intotal MPs, PMPs and T-LyMPs at the baseline between the 2 groups. While total MPs, PMPs and T-LyMPs in the iPD group were significantly higher than those in the iOR group after immunotherapy(P < 0.05). In the multivariate logistic regression analysis, PMPs ≥80 events/µL after immunotherapy(OR, 7.270; 95% CI, 1.092-48.404, P = 0.04) were associated with disease progression in advanced NSCLC and could independently predict the therapeutic effect of immunotherapy.Conclusions:PMPs after immunotherapy independently predicted the therapeutic effects of ICIs, making it possible to monitor the therapeutic effect in real time and rapidly adjust treatment regimens. In addition, this study found for the first time that elevated circulating T-LyMPs were associated with disease progression in advanced NSCLC.

Biomarkers of Platelet Activation and Their Prognostic Value in Patients With Sepsis-Associated Disseminated Intravascular Coagulopathy

Sepsis-associated disseminated intravascular coagulation (DIC) is related to marked hemostatic changes such as transient thrombocytopenia secondary to the endogenous activation and consumption of platelets. This study measured markers of platelet function in 103 adult ICU patients with clinically established sepsis-associated DIC to determine the biomarker association with disease severity. Patients were categorized as having no DIC, nonovert DIC, or overt DIC using the International Society of Thrombosis and Hemostasis scoring system. Plasma levels of CD40L, platelet factor 4 (PF4), platelet-derived microparticles, and microparticle-associated tissue factor were quantified. Markers of platelet activation were significantly elevated in patients with DIC compared to healthy individuals. This increase was independent of platelet count. Levels of PF4 differed based on the severity of DIC and differentiated nonsurvivors and survivors. These findings suggest that the markers of platelet activation in DIC may not be regulated by the number of circulating platelets and may be independent of the factors leading to their consumption.

Association of Systemic Endothelial-Derived and Platelet-Derived Microparticles With Clinical Outcomes in Chronic Obstructive Pulmonary Disease.

Endothelial and platelet microparticles (eMPs and pMPs), markers of cellular activation, dysfunction, or apoptosis, have been associated with multiple cardiovascular conditions. Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular comorbidities and platelet/endothelial dysfunction. We analyzed whether eMPs and pMPs are associated with COPD status and/or severity. A total of 58 COPD patients and 19 controls were enrolled and followed for an average of 1.17 years. Characterization of COPD included lung function, Body mass index-airflow Obstruction-Dyspnea-Exercise (BODE) scores, health-related quality of life, exacerbations, comorbidities, and mortality. Plasma collection to measure eMPs and pMPs via flow cytometry was performed at enrollment as well as during acute exacerbation in 17 participants. We measured pMPs (CD31+, CD41+31+, CD 62P+), eMPs (ULEX lectin+, CD51+, CD54+, CD62E+), the apoptotic CD62E+/CD31+ ratio, and Annexin V MP. As a group, COPD participants had no difference in all MP levels studied compared with controls. No significant correlations with diffusion capacity for carbon monoxide, quality of life, and exacerbation status were found in all MPs studied. However, the eMP ULEX and the pMP CD 62P+ were higher among COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stage 3 patients compared to controls. The CD62E+/CD31+ ratio was lower in controls and GOLD stage 1 COPD participants compared with GOLD stage 2/3 COPD participants, suggesting increased apoptosis. eMP ULEX lectin+ decreased during acute exacerbations and pMP41+31+ significantly increased as BODE score increased. After adjusting for comorbidities, most eMPs and pMPs studied do not correlate significantly with COPD status or severity.

Efficacy of Different Fluid Resuscitation Methods on Coagulation Function of Rats with Traumatic Hemorrhagic Shock

BackgroundFluid resuscitation is widely used for treating traumatic hemorrhagic shock. We focused on the efficacies of different fluid resuscitation methods on improving coagulation function of traumatic hemorrhagic shock (THS) rats. Materials and methodsSprague-Dawley rats (n = 100) were randomly divided into 5 groups, namely, Sham group, THS group, acetic acid Ringer's fluid (AR) group, hydroxyethyl starch solution (HES) group, and AR + HES group. A THS rat model was established by left femoral bleeding. The effects of different fluid resuscitation methods on conventional coagulation function parameters, Rotational thromboelastometry parameters, platelet-derived microparticles and endothelial cell–derived microparticles content of the THS rats were detected by ACL TOP system, rotation thromboelastometry, and flow cytometry, respectively. ResultsUsing AR and HES alone had no significant effect on the coagulation function of THS rats, but the two in combination reduced the increases of thrombin time, prothrombin time, activated part thrombin time, international normalized ratio, fibrin degradation products, D-dimer and the decreases of platelet count and fibrinogen concentration induced by THS. The CT and CFT were significantly reduced, whereas α and MCF were increased in the THS rats in AR + HES group. The combination of AR and HES reversed the effect of THS on elevating platelet-derived microparticles and endothelial cell–derived microparticle levels. In addition, the coagulation was relatively the optimal in the AR, HES, and AR + HES groups when the mice were resuscitated to a mean arterial pressure of 60 mmHg. ConclusionsAR combined with HES has a significant protective effect on coagulation function of THS rats when the mean arterial pressure reaches 60 mmHg.

Inter-Relationship between Platelet-Derived Microparticles and Oxidative Stress in Patients with Venous Thromboembolism.

Background: Hypercoagulative conditions play a key role in venous thromboembolism (VTE). Inflammation is currently linked to VTE, but the potential role of circulating microparticles and oxidative stress (OxS) must be elucidated. The aim of this study was to evaluate platelet-derived microparticles and surrogate OxS biomarkers in patients diagnosed with VTE through a case–control study. Methods: Platelet-derived microparticles (MPs), pro-thrombinase-induced clotting time assay (PiCT), phospholipids (PLPs), malondialdehyde (MDA), 4-hydroxynonenale (4-HNE), thiobarbituric acid reactive substances (TBARs), superoxide dismutase (SOD), and galectin-3 (Gal-3) were measured in VTE patients and in healthy controls. Results: PLPs, 4-HNE, TBARs, and Gal-3 were higher in VTE patients compared to controls; conversely, SOD was lower. A significant non-linear regression between OxS biomarkers and the markers of platelet degranulation was found. Conclusion: Our results suggest that OxS and platelet degranulation are concomitant pathophysiological mechanisms in VTE.

Platelet-derived calpain cleaves the endothelial protease-activated receptor 1 to induce vascular inflammation in diabetes

Diabetes mellitus is a major risk factor for cardiovascular disease. Platelets from diabetic patients are hyperreactive and release microparticles that carry activated cysteine proteases or calpains. Whether platelet-derived calpains contribute to the development of vascular complications in diabetes is unknown. Here we report that platelet-derived calpain1 (CAPN1) cleaves the protease-activated receptor 1 (PAR-1) on the surface of endothelial cells, which then initiates a signaling cascade that includes the activation of the tumor necrosis factor (TNF)-α converting enzyme (TACE). The latter elicits the shedding of the endothelial protein C receptor and the generation of TNF-α, which in turn, induces intracellular adhesion molecule (ICAM)-1 expression to promote monocyte adhesion. All of the effects of CAPN1 were mimicked by platelet-derived microparticles from diabetic patients or from wild-type mice but not from CAPN1−/− mice, and were not observed in PAR-1-deficient endothelial cells. Importantly, aortae from diabetic mice expressed less PAR-1 but more ICAM-1 than non-diabetic mice, effects that were prevented by treating diabetic mice with a calpain inhibitor as well as by the platelet specific deletion of CAPN1. Thus, platelet-derived CAPN1 contributes to the initiation of the sterile vascular inflammation associated with diabetes via the cleavage of PAR-1 and the release of TNF-α from the endothelial cell surface.

Microfluidic Devices: High‐Throughput Separation of Microvesicles from Whole Blood Components Using Viscoelastic Fluid (Adv. Mater. Technol. 12/2020)

In article number 2000612, Jeonghun Nam, Chae Seung Lim, and co-workers demonstrate a sheathless, label-free, viscoelastic microfluidic device for separation of submicrometer microvesicles (MVs) from whole blood. This device enables the isolation of platelet-derived microparticles (PDMPs) from diluted whole blood sample without platelet activation. It can be expected that the device can be used as a standard protocol, enabling high-recovery and high-sensitivity isolation of MVs shed from not only blood cells, but also bacteria, viruses, or cancer, for disease diagnosis in clinical settings.

Synergistic effects of EMPs and PMPs on pulmonary vascular leakage and lung injury after ischemia/reperfusion

BackgroundVascular leakage is an important pathophysiological process of critical conditions such as shock and ischemia–reperfusion (I/R)-induced lung injury. Microparticles (MPs), including endothelial cell-derived microparticles (EMPs), platelet-derived microparticles (PMPs) and leukocyte-derived microparticles (LMPs), have been shown to participate in many diseases. Whether and which of these MPs take part in pulmonary vascular leakage and lung injury after I/R and whether these MPs have synergistic effect and the underlying mechanism are not known.MethodsUsing hemorrhage/transfusion (Hemo/Trans) and aorta abdominalis occlusion-induced I/R rat models, the role of EMPs, PMPs and LMPs and the mechanisms in pulmonary vascular leakage and lung injury were observed.ResultsThe concentrations of EMPs, PMPs and LMPs were significantly increased after I/R. Intravenous administration of EMPs and PMPs but not LMPs induced pulmonary vascular leakage and lung injury. Furthermore, EMPs induced pulmonary sequestration of platelets and promoted more PMPs production, and played a synergistic effect on pulmonary vascular leakage. MiR-1, miR-155 and miR-542 in EMPs, and miR-126 and miR-29 in PMPs, were significantly increased after hypoxia/reoxygenation (H/R). Of which, inhibition of miR-155 in EMPs and miR-126 in PMPs alleviated the detrimental effects of EMPs and PMPs on vascular barrier function and lung injury. Overexpression of miR-155 in EMPs down-regulated the expression of tight junction related proteins such as ZO-1 and claudin-5, while overexpression of miR-126 up-regulated the expression of caveolin-1 (Cav-1), the trans-cellular transportation related protein such as caveolin-1 (Cav-1). Inhibiting EMPs and PMPs production with blebbistatin (BLE) and amitriptyline (AMI) alleviated I/R induced pulmonary vascular leakage and lung injury.ConclusionsEMPs and PMPs contribute to the pulmonary vascular leakage and lung injury after I/R. EMPs mediate pulmonary sequestration of platelets, producing more PMPs to play synergistic effect. Mechanically, EMPs carrying miR-155 that down-regulates ZO-1 and claudin-5 and PMPs carrying miR-126 that up-regulates Cav-1, synergistically mediate pulmonary vascular leakage and lung injury after I/R.Graphic abstract8k8MRpqBub_wL9wmZ4ez89Video

Inflammatory cytokines enhance procoagulant activity of platelets and endothelial cells through phosphatidylserine exposure in patients with essential hypertension.

The exact mechanism of the prothrombotic state of essential hypertension (EH) patients remains elusive. Our objective was to assess whether phosphatidylserine (PS) exposure on endothelial cells (ECs), platelets, and microparticles (MPs) can account for the hypercoagulability in EH patients. PS exposure on cells and MPs, mainly from platelets and ECs was analyzed with flow cytometry. Procoagulant activity (PCA) was evaluated by purified coagulation complex assays, clotting time, and fibrin turbidity. We found that EH patients exhibited elevated levels of PS+ platelets, serum-cultured ECs, MPs, endothelial-derived MPs and platelet-derived MPs compared to the controls (all P < 0.05). Moreover, platelets and MPs from the patients and their sera-cultured ECs showed markedly enhanced intrinsic/extrinsic FXa, thrombin, and fibrin generation, and greatly shortened coagulation time. This PCA could be blocked approximately 80%, by the addition of lactadherin. Furthermore, we detected elevated levels of IL-8, IL-6, and TNF-α in EH patients could activate platelets/ECs and induce elevated PS exposure on their membranes. Our results suggest that inflammatory cytokines could enhance procoagulant activity of platelets and endothelial cells via their PS exposure in EH patients. As such, a PS blockade may be a viable therapeutic strategy for treating such patients.

High‐Throughput Separation of Microvesicles from Whole Blood Components Using Viscoelastic Fluid

AbstractCell‐derived microvesicles (MVs, also known as microparticles, MPs) are known as important biomarkers of various diseases including cardiovascular diseases, infectious diseases, and cancer. Development of techniques for blood cell removal and MV isolation is required for downstream analyses in biological and clinical applications. A sheathless, label‐free, viscoelastic microfluidic device is proposed for the separation of submicrometer platelet‐derived MPs (PDMPs) from whole blood. Flow rate and channel length dependent performance of the device is evaluated using 2‐µm particles as analogs to platelets and hematocrit (Hct) dependent flow characteristics of red blood cells (RBCs) are observed. In addition, the removal rate of nanoparticles of sizes 300, 500, 700, and 1000 nm is evaluated, and finally, the device is applied to examine the recovery of PDMPs from diluted whole blood sample. At Q = 200 µL min−1 in a 15‐mm long microchannel, RBCs at 5% Hct and platelets are removed to the central outlet without platelet activation, while PDMPs are successfully isolated to the side outlets within ≈2 min. The PDMPs collected from the device are analyzed by flow cytometry. The device exhibits ≈4.8‐fold enhanced isolation performance compared to the centrifugation method.

Platelet Microparticle Controversial Role in Cancer.

Platelet-derived microparticles (PMPs) are a group of micrometer-scale extracellular vesicles released by platelets upon activation that are responsible for the majority of microvesicles found in plasma. PMPs’ physiological properties and functions have long been investigated by researchers. In this regard, a noticeable area of studies has been devoted to evaluating the potential roles and effects of PMPs on cancer progression. Clinical and experimental evidence conflictingly implicates supportive and suppressive functions for PMPs regarding cancer. Many of these functions could be deemed as a cornerstone for future considerations of PMPs usage in cancer targeted therapy. This review discusses what is currently known about PMPs and provides insights for new and possible research directions for further grasping the intricate interplay between PMPs and cancer.

Platelet-Derived Microparticles (MPs) and Thrombin Generation Velocity in Deep Vein Thrombosis (DVT): Results of a Case-Control Study.

IntroductionThe role of platelets (Ps) and platelet-derived microparticles (MPs) in venous thromboembolism (VTE) is still being debated.MethodsWe measured MPs, velocity of thrombin formation (PiCT) and phospholipid generation (PLPs) in 40 patients with unprovoked deep vein thrombosis (DVT), who were compared with 40 healthy controls.ResultsMPs were higher in DVT (7.12 nM; 25th–75th percentile 5.26–9.12) than in controls (5.45 nM; 25th–75th percentile 1.67–8.96) (p = 0.19). PiCT velocity was lower in DVT (1.87 sec; 25th–75th percentile 1.75–1.93 sec) compared with controls (1.95 sec; 25th–75th percentile 1.84–2.24 sec) (p = 0.04). PLPs were higher in DVT (77.03 µg/mL; 25th–75th percentile 72.12–103.59 µg/mL) compared with controls (68.65 µg/mL, 25th–75th percentile 55.31–78.20 µg/mL) (p = 0.02).DiscussionWe hypothesize that MPs could be integrated with the lab network assay in evaluating Ps’ role as an activated procoagulative condition. We encourage research on Ps and P-derived microvesicle pathways in patients with unprovoked DVT and not only in patients with cancer-induced DVT.

Platelet-derived microparticles enhance megakaryocyte differentiation and platelet generation via miR-1915-3p

Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production.