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11 pages, 1771 KiB

Open AccessArticle

Ethyl Hydroxyethyl Cellulose—A Biocompatible Polymer Carrier in Blood

by Anja Eckelt, Franziska Wichmann, Franziska Bayer, John Eckelt, Jonathan Groß, Till Opatz, Kerstin Jurk, Christoph Reinhardt and Klytaimnistra Kiouptsi

Int. J. Mol. Sci. 2022, 23(12), 6432; https://doi.org/10.3390/ijms23126432 - 9 Jun 2022

Cited by 2 | Viewed by 2116

Abstract

The biocompatibility of carrier nanomaterials in blood is largely hampered by their activating or inhibiting role on the clotting system, which in many cases prevents safe intravascular application. Here, we characterized an aqueous colloidal ethyl hydroxyethyl cellulose (EHEC) solution and tested its effect [...] Read more.

The biocompatibility of carrier nanomaterials in blood is largely hampered by their activating or inhibiting role on the clotting system, which in many cases prevents safe intravascular application. Here, we characterized an aqueous colloidal ethyl hydroxyethyl cellulose (EHEC) solution and tested its effect on ex vivo clot formation, platelet aggregation, and activation by thromboelastometry, aggregometry, and flow cytometry. We compared the impact of EHEC solution on platelet aggregation with biocompatible materials used in transfusion medicine (the plasma expanders gelatin polysuccinate and hydroxyethyl starch). We demonstrate that the EHEC solution, in contrast to commercial products exhibiting Newtonian flow behavior, resembles the shear-thinning behavior of human blood. Similar to established nanomaterials that are considered biocompatible when added to blood, the EHEC exposure of resting platelets in platelet-rich plasma does not enhance tissue thromboplastin- or ellagic acid-induced blood clotting, or platelet aggregation or activation, as measured by integrin α_IIbβ₃ activation and P-selectin exposure. Furthermore, the addition of EHEC solution to adenosine diphosphate (ADP)-stimulated platelet-rich plasma does not affect the platelet aggregation induced by this agonist. Overall, our results suggest that EHEC may be suitable as a biocompatible carrier material in blood circulation and for applications in flow-dependent diagnostics. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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13 pages, 1581 KiB

Open AccessArticle

Increase of Circulating Monocyte–Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage

by Anaís Mariscal, Carlos Zamora, César Díaz-Torné, Mᵃ Àngels Ortiz, Juan José de Agustín, Delia Reina, Paula Estrada, Patricia Moya, Héctor Corominas and Sílvia Vidal

Int. J. Mol. Sci. 2022, 23(10), 5748; https://doi.org/10.3390/ijms23105748 - 20 May 2022

Cited by 4 | Viewed by 2647

Abstract

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). [...] Read more.

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte–PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte–PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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13 pages, 3073 KiB

Open AccessArticle

Human Platelets Contain, Translate, and Secrete Azurocidin; A Novel Effect on Hemostasis

by Alba Soledad Aquino-Domínguez, Víctor Acevedo-Sánchez, Diego Sait Cruz-Hernández, Saraí Remedios Sánchez-Aparicio, María de los Ángeles Romero-Tlalolini, Rafael Baltiérrez-Hoyos, Luis Manuel Sánchez-Navarro, Honorio Torres-Aguilar, José Bustos-Arriaga and Sergio Roberto Aguilar-Ruiz

Int. J. Mol. Sci. 2022, 23(10), 5667; https://doi.org/10.3390/ijms23105667 - 18 May 2022

Cited by 1 | Viewed by 2521

Abstract

Platelets play a significant role in hemostasis and perform essential immune functions, evidenced by the extensive repertoire of antimicrobial molecules. Currently, there is no clear description of the presence of azurocidin in human platelets. Azurocidin is a 37 kDa cationic protein abundant in [...] Read more.

Platelets play a significant role in hemostasis and perform essential immune functions, evidenced by the extensive repertoire of antimicrobial molecules. Currently, there is no clear description of the presence of azurocidin in human platelets. Azurocidin is a 37 kDa cationic protein abundant in neutrophils, with microbicidal, opsonizing, and vascular permeability-inducing activity. Therefore, this work aimed to characterize the content, secretion, translation, and functions of azurocidin in platelets. Our results show the presence of azurocidin mRNA and protein in α-granules of platelet and megakaryoblasts, and stimulation with thrombin, ADP, and LPS leads to the secretion of free azurocidin as well as within extracellular vesicles. In addition, platelets can translate azurocidin in a basal or thrombin-induced manner. Finally, we found that the addition of low concentrations of azurocidin prevents platelet aggregation and activation. In conclusion, we demonstrate that platelets contain, secrete, and translate azurocidin, and this protein may have important implications for hemostasis. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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14 pages, 2716 KiB

Open AccessArticle

Platelet Extracellular Vesicles Are Taken up by Canine T Lymphocytes but Do Not Play a Role in Their Proliferation, Differentiation and Cytokine Production In Vitro

by Magdalena Żmigrodzka, Olga Witkowska-Piłaszewicz, Rafał Pingwara and Anna Winnicka

Int. J. Mol. Sci. 2022, 23(10), 5504; https://doi.org/10.3390/ijms23105504 - 14 May 2022

Cited by 4 | Viewed by 2288

Abstract

Eukaryotic and prokaryotic cells in physiological and pathological conditions form membrane-bound extracellular vesicles, known as EVs. The ability of these submicron structures to transfer their cargoes (miRNA, DNA, protein, cytokines, receptors, etc.) into recipient cells is described. Recent data revealed that platelet-derived extracellular [...] Read more.

Eukaryotic and prokaryotic cells in physiological and pathological conditions form membrane-bound extracellular vesicles, known as EVs. The ability of these submicron structures to transfer their cargoes (miRNA, DNA, protein, cytokines, receptors, etc.) into recipient cells is described. Recent data revealed that platelet-derived extracellular vesicles (PEVs) crosstalk promotes cancer growth and metastasis formation. Moreover, they exert immunosuppressive activities on phagocytes. This EV subpopulation is the most abundant amongst all types in circulation. According to the authors’ best knowledge, there is no information regarding the impact of PEVs on canine lymphocytes. The aim of this study was to evaluate the influence of PEVs on lymphocyte proliferation, phenotype and cytokine production in vitro. In the study, it was demonstrated (i) that PEVs interact differently with lymphocyte subsets and are preferentially associated with T-lymphocytes PBMC, while (ii) they are rarely detected in association with B-lymphocytes, and there is evidence that (iii) PEV uptake is observed after 7 h of co-culturing with lymphocytes. In addition, obtained data support the notion that PEVs do not influence in vitro lymphocyte proliferation, differentiation and cytokine production in a canine model. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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20 pages, 2441 KiB

Open AccessArticle

Potential Role of Mitochondria as Modulators of Blood Platelet Activation and Reactivity in Diabetes and Effect of Metformin on Blood Platelet Bioenergetics and Platelet Activation

by Karolina Siewiera, Magdalena Labieniec-Watala, Hassan Kassassir, Nina Wolska, Dawid Polak and Cezary Watala

Int. J. Mol. Sci. 2022, 23(7), 3666; https://doi.org/10.3390/ijms23073666 - 27 Mar 2022

Cited by 7 | Viewed by 2975

Abstract

Blood platelet dysfunctions are strongly involved in the development of the micro- and macrovascular complications in diabetes mellitus (DM). However, the molecular causes of abnormal platelet activation in DM remain unclear. Experimental data suggests that platelet mitochondria can regulate the prothrombotic phenotype of [...] Read more.

Blood platelet dysfunctions are strongly involved in the development of the micro- and macrovascular complications in diabetes mellitus (DM). However, the molecular causes of abnormal platelet activation in DM remain unclear. Experimental data suggests that platelet mitochondria can regulate the prothrombotic phenotype of platelets, and changes in these organelles may influence platelet activation and modify platelet responses to stimulation. The present study evaluates the impact of DM on mitochondrial respiratory parameters and blood platelet activation/reactivity in a rat model of experimental diabetes following 1, 2.5 and 5 months of streptozotocin (STZ)-induced diabetes. Moreover, a mild inhibition of the mitochondrial respiratory chain with the use of metformin under in vitro and in vivo conditions was tested as a method to reduce platelet activation and reactivity. The platelets were studied with a combination of flow cytometry and advanced respirometry. Our results indicate that prolonged exposure of blood platelets to high concentrations of glucose, as in diabetes, can result in elevated blood platelet mitochondrial respiration; this may be an effect of cell adaptation to the high availability of energy substrates. However, as these alterations occur later than the changes in platelet activation/reactivity, they may not constitute the major reason for abnormal platelet functioning in DM. Moreover, metformin was not able to inhibit platelet activation and reactivity under in vitro conditions despite causing a decrease in mitochondrial respiration. This indicates that the beneficial effect of metformin on the coagulation system observed in vivo can be related to other mechanisms than via the inhibition of platelet activation. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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11 pages, 2204 KiB

Open AccessArticle

Platelets Purification Is a Crucial Step for Transcriptomic Analysis

by Mohamad Chebbo, Said Assou, Veronique Pantesco, Catherine Duez, Marie C. Alessi, Pascal Chanez and Delphine Gras

Int. J. Mol. Sci. 2022, 23(6), 3100; https://doi.org/10.3390/ijms23063100 - 13 Mar 2022

Cited by 9 | Viewed by 3497

Abstract

Platelets are small anucleate cells derived from the fragmentation of megakaryocytes and are involved in different biological processes especially hemostasis, thrombosis, and immune response. Despite their lack of nucleus, platelets contain a reservoir of megakaryocyte-derived RNAs and all the machinery useful for mRNA [...] Read more.

Platelets are small anucleate cells derived from the fragmentation of megakaryocytes and are involved in different biological processes especially hemostasis, thrombosis, and immune response. Despite their lack of nucleus, platelets contain a reservoir of megakaryocyte-derived RNAs and all the machinery useful for mRNA translation. Interestingly, platelet transcriptome was analyzed in health and diseases and led to the identification of disease-specific molecular signatures. Platelet contamination by leukocytes and erythrocytes during platelet purification is a major problem in transcriptomic analysis and the presence of few contaminants in platelet preparation could strongly alter transcriptome results. Since contaminant impacts on platelet transcriptome remains theoretical, we aimed to determine whether low leukocyte and erythrocyte contamination could cause great or only minor changes in platelet transcriptome. Using microarray technique, we compared the transcriptome of platelets from the same donor, purified by common centrifugation method or using magnetic microbeads to eliminate contaminating cells. We found that platelet transcriptome was greatly altered by contaminants, as the relative amount of 8274 transcripts was different between compared samples. We observed an increase of transcripts related to leukocytes and erythrocytes in platelet purified without microbeads, while platelet specific transcripts were falsely reduced. In conclusion, serious precautions should be taken during platelet purification process for transcriptomic analysis, in order to avoid platelets contamination and result alteration. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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12 pages, 2145 KiB

Open AccessArticle

Platelet-Released Growth Factors Influence Wound Healing-Associated Genes in Human Keratinocytes and Ex Vivo Skin Explants

by Michael Singh, Serhat Akkaya, Mark Preuß, Franziska Rademacher, Mersedeh Tohidnezhad, Yusuke Kubo, Peter Behrendt, Jan-Tobias Weitkamp, Thilo Wedel, Ralph Lucius, Regine Gläser, Jürgen Harder and Andreas Bayer

Int. J. Mol. Sci. 2022, 23(5), 2827; https://doi.org/10.3390/ijms23052827 - 4 Mar 2022

Cited by 9 | Viewed by 2536

Abstract

Platelet-released growth factors (PRGFs) or other thrombocyte concentrate products, e.g., Platelet-Rich Fibrin (PRF), have become efficient tools of regenerative medicine in many medical disciplines. In the context of wound healing, it has been demonstrated that treatment of chronic or complicated wounds with PRGF [...] Read more.

Platelet-released growth factors (PRGFs) or other thrombocyte concentrate products, e.g., Platelet-Rich Fibrin (PRF), have become efficient tools of regenerative medicine in many medical disciplines. In the context of wound healing, it has been demonstrated that treatment of chronic or complicated wounds with PRGF or PRF improves wound healing in the majority of treated patients. Nevertheless, the underlying cellular and molecular mechanism are still poorly understood. Therefore, we aimed to analyze if PRGF-treatment of human keratinocytes caused the induction of genes encoding paracrine factors associated with successful wound healing. The investigated genes were Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDGFB). We observed a significant gene induction of SEMA7A, ANGPLT4, FGF-2, IL-32, MMP-2 and PDGFB in human keratinocytes after PRGF treatment. The CCL20- and CXCL10 gene expressions were significantly inhibited by PRGF therapy. Signal transduction analyses revealed that the PRGF-mediated gene induction of SEMA7A, ANGPLT4, IL-32 and MMP-2 in human keratinocytes was transduced via the IL-6 receptor pathway. In contrast, EGF receptor signaling was not involved in the PRGF-mediated gene expression of analyzed genes in human keratinocytes. Additionally, treatment of ex vivo skin explants with PRGF confirmed a significant gene induction of SEMA7A, ANGPLT4, MMP-2 and PDGFB. Taken together, these results describe a new mechanism that could be responsible for the beneficial wound healing properties of PRGF or related thrombocytes concentrate products such as PRF. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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16 pages, 2463 KiB

Open AccessArticle

Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts

by Andreas Bayer, Bernard Wijaya, Franziska Rademacher, Lena Möbus, Mark Preuß, Michael Singh, Mersedeh Tohidnezhad, Yusuke Kubo, Meno Rodewald, Peter Behrendt, Jan-Tobias Weitkamp, Regine Gläser and Jürgen Harder

Int. J. Mol. Sci. 2021, 22(19), 10536; https://doi.org/10.3390/ijms221910536 - 29 Sep 2021

Cited by 5 | Viewed by 2695

Abstract

Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms [...] Read more.

Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms have been insufficiently investigated. Therefore, we analyzed the influence of Platelet-Released Growth Factors (PRGF) on human dermal fibroblasts. Whole transcriptome sequencing and gene ontology (GO) enrichment analysis of PRGF-treated fibroblasts revealed an induction of several genes involved in the formation of the extracellular matrix (ECM). Real-time PCR analyses of PRGF-treated fibroblasts and skin explants confirmed the induction of ECM-related genes, in particular transforming growth factor beta-induced protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), a disintegrin and metalloproteinase 19 (ADAM19), serpin family E member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3). The induction of these genes was time-dependent and in part influenced by the epidermal growth factor receptor (EGFR). Moreover, PRGF induced migration and proliferation of the fibroblasts. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound-healing effects of thrombocyte concentrate products. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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11 pages, 2420 KiB

Open AccessArticle

Platelet Inhibition Prevents NLRP3 Inflammasome Activation and Sepsis-Induced Kidney Injury

by Marivee Borges-Rodriguez, Corbin A. Shields, Olivia K. Travis, Robert W. Tramel, Cedar H. Baik, Chelsea A. Giachelli, Geilda A. Tardo, Jan Michael Williams and Denise C. Cornelius

Int. J. Mol. Sci. 2021, 22(19), 10330; https://doi.org/10.3390/ijms221910330 - 25 Sep 2021

Cited by 24 | Viewed by 3406

Abstract

Platelets, cellular mediators of thrombosis, are activated during sepsis and are increasingly recognized as mediators of the immune response. Platelet activation is significantly increased in sepsis patients compared to ICU control patients. Despite this correlation, the role of activated platelets in contributing to [...] Read more.

Platelets, cellular mediators of thrombosis, are activated during sepsis and are increasingly recognized as mediators of the immune response. Platelet activation is significantly increased in sepsis patients compared to ICU control patients. Despite this correlation, the role of activated platelets in contributing to sepsis pathophysiology remains unclear. We previously demonstrated NOD-like receptor protein 3 inflammasome (NLRP3) inflammasome activation in sepsis-induced platelets from cecal-ligation puncture (CLP) rats. Activated platelets were associated with increased pulmonary edema and glomerular injury in CLP vs. SHAM controls. In this study, we investigated whether inhibition of platelet activation would attenuate NLRP3 activation and renal and pulmonary injury in response to CLP. CLP was performed in male and female Sprague Dawley (SD) rats (n = 10/group) to induce abdominal sepsis and SHAM rats served as controls. A subset of CLP animals was treated with Clopidogrel (10 mg/kg/day, CLP + CLOP) to inhibit platelet activation. At 72 h post-CLP, platelet activation and NLRP3 inflammasome assembly were evaluated, IL-1β and IL-18 were measured in plasma, and tissues, renal and pulmonary pathology, and renal function were assessed. Activated platelets were 7.8 ± 3.6% in Sham, 22 ± 6% in CLP and significantly decreased to 14.5 ± 0.6% in CLP + CLOP (n = 8–10/group, p < 0.05). NLRP3 inflammasome assembly was inhibited in platelets of CLP + CLOP animals vs. CLP. Significant increases in plasma and kidney IL-1β and IL-18 in response to CLP were decreased with Clopidogrel treatment. Renal injury, but not lung histology or renal function was improved in CLP + CLOP vs. CLP. These data provide evidence that activated platelets may contribute to sepsis-induced renal injury, possibly via NLRP3 activation in platelets. Platelets may be a therapeutic target to decrease renal injury in septic patients. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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13 pages, 3828 KiB

Open AccessCommunication

Utility of Platelet Endothelial Cell Adhesion Molecule 1 in the Platelet Activity Assessment in Mouse and Human Blood

by Natalia Marcinczyk, Tomasz Misztal, Anna Gromotowicz-Poplawska, Agnieszka Zebrowska, Tomasz Rusak, Piotr Radziwon and Ewa Chabielska

Int. J. Mol. Sci. 2021, 22(17), 9611; https://doi.org/10.3390/ijms22179611 - 4 Sep 2021

Cited by 9 | Viewed by 2806

Abstract

In our previous study, we introduced the platelet endothelial cell adhesion molecule 1 (PECAM-1)/thrombus ratio, which is a parameter indicating the proportion of PECAM-1 in laser-induced thrombi in mice. Because PECAM-1 is an antithrombotic molecule, the higher the PECAM-1/thrombus ratio, the less activated [...] Read more.

In our previous study, we introduced the platelet endothelial cell adhesion molecule 1 (PECAM-1)/thrombus ratio, which is a parameter indicating the proportion of PECAM-1 in laser-induced thrombi in mice. Because PECAM-1 is an antithrombotic molecule, the higher the PECAM-1/thrombus ratio, the less activated the platelets. In this study, we used an extracorporeal model of thrombosis (flow chamber model) to verify its usefulness in the assessment of the PECAM-1/thrombus ratio in animal and human studies. Using the lipopolysaccharide (LPS)-induced inflammation model, we also evaluated whether the PECAM-1/thrombus ratio determined in the flow chamber (without endothelium) differed from that calculated in laser-induced thrombosis (with endothelium). We observed that acetylsalicylic acid (ASA) decreased the area of the thrombus while increasing the PECAM-1/thrombus ratio in healthy mice and humans in a dose-dependent manner. In LPS-treated mice, the PECAM-1/thrombus ratio decreased as the dose of ASA increased in both thrombosis models, but the direction of change in the thrombus area was inconsistent. Our study demonstrates that the PECAM-1/thrombus ratio can more accurately describe the platelet activation status than commonly used parameters such as the thrombus area, and, hence, it can be used in both human and animal studies. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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14 pages, 2665 KiB

Open AccessArticle

The Proteasome Inhibitor Bortezomib Induces Apoptosis and Activation in Gel-Filtered Human Platelets

by Harriet Ghansah, Ildikó Beke Debreceni, Zsolt Fejes, Béla Nagy, Jr. and János Kappelmayer

Int. J. Mol. Sci. 2021, 22(16), 8955; https://doi.org/10.3390/ijms22168955 - 19 Aug 2021

Cited by 3 | Viewed by 2445

Abstract

Bortezomib (BTZ) has demonstrated its efficacy in several hematological disorders and has been associated with thrombocytopenia. There is controversy about the effect of BTZ on human platelets, so we set out to determine its effect on various types of platelet samples. Human platelets [...] Read more.

Bortezomib (BTZ) has demonstrated its efficacy in several hematological disorders and has been associated with thrombocytopenia. There is controversy about the effect of BTZ on human platelets, so we set out to determine its effect on various types of platelet samples. Human platelets were investigated in platelet-rich plasma (PRP) and as gel-filtered platelets (GFPs). Mitochondrial inner membrane potential depolarization and phosphatidylserine (PS) and P-selectin expression levels were studied by flow cytometry, while thrombin generation was measured by a fluorescent method. In PRP, BTZ caused negligible PS expression after 60 min of treatment. However, in GFPs, PS expression was dose- and time-dependently increased in the BTZ-treated groups, as was P-selectin. The percentage of depolarized cells was also higher after BTZ pretreatment at both time points. Peak thrombin and velocity index increased significantly even with the lowest BTZ concentration (p = 0.0019; p = 0.0032) whereas time to peak and start tail parameters decreased (p = 0.0007; p = 0.0034). The difference between PRP and GFP results can be attributed to the presence of plasma proteins in PRP, as the PS-stimulating effect of BTZ could be attenuated by supplementing GFPs with purified human albumin. Overall, BTZ induces a procoagulant platelet phenotype in an experimental setting devoid of plasma proteins. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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16 pages, 2675 KiB

Open AccessArticle

Effects of Cancer Presence and Therapy on the Platelet Proteome

by Maudy Walraven, Siamack Sabrkhany, Jaco C. Knol, Henk Dekker, Inge de Reus, Sander R. Piersma, Thang V. Pham, Arjan W. Griffioen, Henk J. Broxterman, Mirjam Oude Egbrink, Henk M. W. Verheul and Connie R. Jimenez

Int. J. Mol. Sci. 2021, 22(15), 8236; https://doi.org/10.3390/ijms22158236 - 30 Jul 2021

Cited by 11 | Viewed by 3758

Abstract

Platelets are involved in tumor angiogenesis and cancer progression. Previous studies indicated that cancer could affect platelet content. In the current study, we investigated whether cancer-associated proteins can be discerned in the platelets of cancer patients, and whether antitumor treatment may affect the [...] Read more.

Platelets are involved in tumor angiogenesis and cancer progression. Previous studies indicated that cancer could affect platelet content. In the current study, we investigated whether cancer-associated proteins can be discerned in the platelets of cancer patients, and whether antitumor treatment may affect the platelet proteome. Platelets were isolated from nine patients with different cancer types and ten healthy volunteers. From three patients, platelets were isolated before and after the start of antitumor treatment. Mass spectrometry-based proteomics of gel-fractionated platelet proteins were used to compare patients versus controls and before and after treatment initiation. A total of 4059 proteins were detected, of which 50 were significantly more abundant in patients, and 36 more in healthy volunteers. Eight of these proteins overlapped with our previous cancer platelet proteomics study. From these data, we selected potential biomarkers of cancer including six upregulated proteins (RNF213, CTSG, PGLYRP1, RPL8, S100A8, S100A9) and two downregulated proteins (GPX1, TNS1). Antitumor treatment resulted in increased levels of 432 proteins and decreased levels of 189 proteins. In conclusion, the platelet proteome may be affected in cancer patients and platelets are a potential source of cancer biomarkers. In addition, we found in a small group of patients that anticancer treatment significantly changes the platelet proteome. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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18 pages, 5121 KiB

Open AccessArticle

Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils, and Mast Cell Degranulation

by Angie De La Cruz, Aubrey Hargrave, Sri Magadi, Justin A. Courson, Paul T. Landry, Wanyu Zhang, Fong W. Lam, Monica A. Bray, C. Wayne Smith, Alan R. Burns and Rolando E. Rumbaut

Int. J. Mol. Sci. 2021, 22(14), 7360; https://doi.org/10.3390/ijms22147360 - 8 Jul 2021

Cited by 4 | Viewed by 3313

Abstract

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β₂-integrin, CD18 (CD18_hypo mice) shows [...] Read more.

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β₂-integrin, CD18 (CD18_hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18_hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (Kit^W-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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13 pages, 2371 KiB

Open AccessArticle

Microelectromechanical System Measurement of Platelet Contraction: Direct Interrogation of Myosin Light Chain Phosphorylation

by Mitchell J. George, Julia Litvinov, Kevin Aroom, Leland J. Spangler, Henry Caplan, Charles E. Wade, Charles S. Cox, Jr. and Brijesh S. Gill

Int. J. Mol. Sci. 2021, 22(12), 6448; https://doi.org/10.3390/ijms22126448 - 16 Jun 2021

Cited by 3 | Viewed by 2704

Abstract

Myosin Light Chain (MLC) regulates platelet contraction through its phosphorylation by Myosin Light Chain Kinase (MLCK) or dephosphorylation by Myosin Light Chain Phosphatase (MLCP). The correlation between platelet contraction force and levels of MLC phosphorylation is unknown. We investigate the relationship between platelet [...] Read more.

Myosin Light Chain (MLC) regulates platelet contraction through its phosphorylation by Myosin Light Chain Kinase (MLCK) or dephosphorylation by Myosin Light Chain Phosphatase (MLCP). The correlation between platelet contraction force and levels of MLC phosphorylation is unknown. We investigate the relationship between platelet contraction force and MLC phosphorylation using a novel microelectromechanical (MEMS) based clot contraction sensor (CCS). The MLCK and MLCP pair were interrogated by inhibitors and activators of platelet function. The CCS was fabricated from silicon using photolithography techniques and force was validated over a range of deflection for different chip spring constants. The force of platelet contraction measured by the clot contraction sensor (CCS) was compared to the degree of MLC phosphorylation by Western Blotting (WB) and ELISA. Stimulators of MLC phosphorylation produced higher contraction force, higher phosphorylated MLC signal in ELISA and higher intensity bands in WB. Inhibitors of MLC phosphorylation produced the opposite. Contraction force is linearly related to levels of phosphorylated MLC. Direct measurements of clot contractile force are possible using a MEMS sensor platform and correlate linearly with the degree of MLC phosphorylation during coagulation. Measured force represents the mechanical output of the actin/myosin motor in platelets regulated by myosin light chain phosphorylation. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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18 pages, 2796 KiB

Open AccessArticle

Age-Dependent Control of Collagen-Dependent Platelet Responses by Thrombospondin-1—Comparative Analysis of Platelets from Neonates, Children, Adolescents, and Adults

by Katrin Herken, Martin Glauner, Stefanie C. Robert, Matthias Maas, Sonja Zippel, Ulrike Nowak-Göttl, Barbara Zieger, Judith Lahav, Anke C. Fender, Kerstin Jurk and Beate E. Kehrel

Int. J. Mol. Sci. 2021, 22(9), 4883; https://doi.org/10.3390/ijms22094883 - 5 May 2021

Cited by 11 | Viewed by 2687

Abstract

Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood. This critical issue remains challenging for the establishment of age-specific reference ranges. In [...] Read more.

Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood. This critical issue remains challenging for the establishment of age-specific reference ranges. In this study, we evaluated platelet reactivity of five pediatric age categories, ranging from healthy full-term neonates up to adolescents (11–18 years) in comparison to healthy adults (>18 years) by flow cytometry. We confirmed that platelet hypo-reactivity detected by fibrinogen binding, P-selectin, and CD63 surface expression was most pronounced in neonates compared to other pediatric age groups. However, maturation of platelet responsiveness varied with age, agonist, and activation marker. In contrast to TRAP and ADP, collagen-induced platelet activation was nearly absent in neonates. Granule secretion markedly remained impaired at least up to 10 years of age compared to adults. We show for the first time that neonatal platelets are deficient in thrombospondin-1, and exogenous platelet-derived thrombospondin-1 allows platelet responsiveness to collagen. Platelets from all pediatric age groups normally responded to the C-terminal thrombospondin-1 peptide RFYVVMWK. Thus, thrombospondin-1 deficiency of neonatal platelets might contribute to the relatively impaired response to collagen, and platelet-derived thrombospondin-1 may control distinct collagen-induced platelet responses. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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17 pages, 3048 KiB

Open AccessArticle

Phenotypic and Functional Consequences of PLT Binding to Monocytes and Its Association with Clinical Features in SLE

by Anaís Mariscal, Carlos Zamora, Berta Magallares, Tarek Carlos Salman-Monte, Mª Àngels Ortiz, Cesar Díaz-Torné, Iván Castellví, Héctor Corominas and Silvia Vidal

Int. J. Mol. Sci. 2021, 22(9), 4719; https://doi.org/10.3390/ijms22094719 - 29 Apr 2021

Cited by 7 | Viewed by 2574

Abstract

Platelets (PLTs) can modulate the immune system through the release of soluble mediators or through interaction with immune cells. Monocytes are the main immune cells that bind with PLTs, and this interaction is increased in several inflammatory and autoimmune conditions, including systemic lupus [...] Read more.

Platelets (PLTs) can modulate the immune system through the release of soluble mediators or through interaction with immune cells. Monocytes are the main immune cells that bind with PLTs, and this interaction is increased in several inflammatory and autoimmune conditions, including systemic lupus erythematosus (SLE). Our aim was to characterize the phenotypic and functional consequences of PLT binding to monocytes in healthy donors (HD) and in SLE and to relate it to the pathogenesis of SLE. We analyzed the phenotypic and functional features of monocytes with non-activated and activated bound PLTs by flow cytometry. We observed that monocytes with bound PLTs and especially those with activated PLTs have an up-regulated HLA-DR, CD86, CD54, CD16 and CD64 expression. Monocytes with bound PLTs also have an increased capacity for phagocytosis, though not for efferocytosis. In addition, monocytes with bound PLTs have increased IL-10, but not TNF-α, secretion. The altered phenotypic and functional features are comparable in SLE and HD monocytes and in bound PLTs. However, the percentages of monocytes with bound PLTs are significantly higher in SLE patients and are associated with undetectable levels of anti-dsDNA antibodies and hematuria, and with normal C3 and albumin/creatinine levels. Our results suggest that PLTs have a modulatory influence on monocytes and that this effect may be highlighted by an increased binding of PLTs to monocytes in autoimmune conditions. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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Review

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29 pages, 2614 KiB

Open AccessReview

The Role of Platelet-Derived Extracellular Vesicles in Immune-Mediated Thrombosis

by Alicia S. Eustes and Sanjana Dayal

Int. J. Mol. Sci. 2022, 23(14), 7837; https://doi.org/10.3390/ijms23147837 - 16 Jul 2022

Cited by 20 | Viewed by 3388

Abstract

Platelet-derived extracellular vesicles (PEVs) play important roles in hemostasis and thrombosis. There are three major types of PEVs described based on their size and characteristics, but newer types may continue to emerge owing to the ongoing improvement in the methodologies and terms used [...] Read more.

Platelet-derived extracellular vesicles (PEVs) play important roles in hemostasis and thrombosis. There are three major types of PEVs described based on their size and characteristics, but newer types may continue to emerge owing to the ongoing improvement in the methodologies and terms used to define various types of EVs. As the literature on EVs is growing, there are continuing attempts to standardize protocols for EV isolation and reach consensus in the field. This review provides information on mechanisms of PEV production, characteristics, cellular interaction, and their pathological role, especially in autoimmune and infectious diseases. We also highlight the mechanisms through which PEVs can activate parent cells in a feedback loop. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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15 pages, 684 KiB

Open AccessReview

Role of Plasminogen Activation System in Platelet Pathophysiology: Emerging Concepts for Translational Applications

by Filomena Napolitano and Nunzia Montuori

Int. J. Mol. Sci. 2022, 23(11), 6065; https://doi.org/10.3390/ijms23116065 - 28 May 2022

Cited by 16 | Viewed by 3601

Abstract

Traditionally, platelets have been exclusively considered for their procoagulant and antifibrinolytic effects during normal activation of hemostasis. Effectively, activated platelets secrete coagulation factors, expose phosphatidylserine, and promote thrombin and fibrin production. In addition to procoagulant activities, platelets confer resistance of thrombi to fibrinolysis [...] Read more.

Traditionally, platelets have been exclusively considered for their procoagulant and antifibrinolytic effects during normal activation of hemostasis. Effectively, activated platelets secrete coagulation factors, expose phosphatidylserine, and promote thrombin and fibrin production. In addition to procoagulant activities, platelets confer resistance of thrombi to fibrinolysis by inducing clot retraction of the fibrin network and release of huge amounts of plasminogen activator inhibitor-1, which is the major physiologic inhibitor of the fibrinolytic cascade. However, the discovery of multiple relations with the fibrinolytic system, also termed Plasminogen Activation System (PAS), has introduced new perspectives on the platelet role in fibrinolysis. Indeed, the activated membrane surface of platelets provides binding sites on which fibrinolytic enzymes can be activated. This review discusses the evidence of the profibrinolytic properties of platelets through the description of PAS components and related proteins that are contained in or bind to platelets. Our analyses of literature data lead to the conclusion that in the initial phase of the hemostatic process, antifibrinolytic effects prevail over profibrinolytic activity, but at later stages, platelets might enhance fibrinolysis through the engagement of PAS components. A better understanding of spatial and temporal characteristics of platelet-mediated fibrinolysis during normal hemostasis could improve therapeutic options for bleeding and thrombotic disorders. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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39 pages, 1578 KiB

Open AccessReview

An Insight into Recent Advances on Platelet Function in Health and Disease

by Preeti Kumari Chaudhary, Sanggu Kim and Soochong Kim

Int. J. Mol. Sci. 2022, 23(11), 6022; https://doi.org/10.3390/ijms23116022 - 27 May 2022

Cited by 40 | Viewed by 11177

Abstract

Platelets play a variety of roles in vascular biology and are best recognized as primary hemostasis and thrombosis mediators. Platelets have a large number of receptors and secretory molecules that are required for platelet functionality. Upon activation, platelets release multiple substances that have [...] Read more.

Platelets play a variety of roles in vascular biology and are best recognized as primary hemostasis and thrombosis mediators. Platelets have a large number of receptors and secretory molecules that are required for platelet functionality. Upon activation, platelets release multiple substances that have the ability to influence both physiological and pathophysiological processes including inflammation, tissue regeneration and repair, cancer progression, and spreading. The involvement of platelets in the progression and seriousness of a variety of disorders other than thrombosis is still being discovered, especially in the areas of inflammation and the immunological response. This review represents an integrated summary of recent advances on the function of platelets in pathophysiology that connects hemostasis, inflammation, and immunological response in health and disease and suggests that antiplatelet treatment might be used for more than only thrombosis. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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23 pages, 1309 KiB

Open AccessReview

Factors Associated with Platelet Activation-Recent Pharmaceutical Approaches

by Panagiotis Theofilis, Marios Sagris, Evangelos Oikonomou, Alexios S. Antonopoulos, Konstantinos Tsioufis and Dimitris Tousoulis

Int. J. Mol. Sci. 2022, 23(6), 3301; https://doi.org/10.3390/ijms23063301 - 18 Mar 2022

Cited by 14 | Viewed by 8226

Abstract

Platelets are at the forefront of human health and disease following the advances in their research presented in past decades. Platelet activation, their most crucial function, although beneficial in the case of vascular injury, may represent the initial step for thrombotic complications characterizing [...] Read more.

Platelets are at the forefront of human health and disease following the advances in their research presented in past decades. Platelet activation, their most crucial function, although beneficial in the case of vascular injury, may represent the initial step for thrombotic complications characterizing various pathologic states, primarily atherosclerotic cardiovascular diseases. In this review, we initially summarize the structural and functional characteristics of platelets. Next, we focus on the process of platelet activation and its associated factors, indicating the potential molecular mechanisms involving inflammation, endothelial dysfunction, and miRs. Finally, an overview of the available antiplatelet agents is being portrayed, together with agents possessing off-set platelet-inhibitory actions, while an extensive presentation of drugs under investigation is being given. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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20 pages, 2457 KiB

Open AccessReview

Prothrombotic Phenotype in COVID-19: Focus on Platelets

by Cristina Barale, Elena Melchionda, Alessandro Morotti and Isabella Russo

Int. J. Mol. Sci. 2021, 22(24), 13638; https://doi.org/10.3390/ijms222413638 - 20 Dec 2021

Cited by 25 | Viewed by 4635

Abstract

COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to [...] Read more.

COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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20 pages, 2997 KiB

Open AccessReview

Recent Advances in the Discovery and Function of Antimicrobial Molecules in Platelets

by Alba S. Aquino-Domínguez, María de los A. Romero-Tlalolini, Honorio Torres-Aguilar and Sergio R. Aguilar-Ruiz

Int. J. Mol. Sci. 2021, 22(19), 10230; https://doi.org/10.3390/ijms221910230 - 23 Sep 2021

Cited by 18 | Viewed by 3639

Abstract

The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation [...] Read more.

The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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14 pages, 626 KiB

Open AccessReview

The Importance of Alpha-Actinin Proteins in Platelet Formation and Function, and Their Causative Role in Congenital Macrothrombocytopenia

by Leanne R. O’Sullivan, Mary R. Cahill and Paul W. Young

Int. J. Mol. Sci. 2021, 22(17), 9363; https://doi.org/10.3390/ijms22179363 - 29 Aug 2021

Cited by 8 | Viewed by 3157

Abstract

The actin cytoskeleton plays a central role in platelet formation and function. Alpha-actinins (actinins) are actin filament crosslinking proteins that are prominently expressed in platelets and have been studied in relation to their role in platelet activation since the 1970s. However, within the [...] Read more.

The actin cytoskeleton plays a central role in platelet formation and function. Alpha-actinins (actinins) are actin filament crosslinking proteins that are prominently expressed in platelets and have been studied in relation to their role in platelet activation since the 1970s. However, within the past decade, several groups have described mutations in ACTN1/actinin-1 that cause congenital macrothrombocytopenia (CMTP)—accounting for approximately 5% of all cases of this condition. These findings are suggestive of potentially novel functions for actinins in platelet formation from megakaryocytes in the bone marrow and/or platelet maturation in circulation. Here, we review some recent insights into the well-known functions of actinins in platelet activation before considering possible roles for actinins in platelet formation that could explain their association with CMTP. We describe what is known about the consequences of CMTP-linked mutations on actinin-1 function at a molecular and cellular level and speculate how these changes might lead to the alterations in platelet count and morphology observed in CMTP patients. Finally, we outline some unanswered questions in this area and how they might be addressed in future studies. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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21 pages, 918 KiB

Open AccessReview

The Use of Total Thrombus Formation Analysis System as a Tool to Assess Platelet Function in Bleeding and Thrombosis Risk—A Systematic Review

by Joanna Sikora, Aleksandra Karczmarska-Wódzka, Joanna Bugieda and Przemysław Sobczak

Int. J. Mol. Sci. 2021, 22(16), 8605; https://doi.org/10.3390/ijms22168605 - 10 Aug 2021

Cited by 12 | Viewed by 2904

Abstract

Background. Today there are many devices that can be used to study blood clotting disorders by identifying abnormalities in blood platelets. The Total Thrombus Formation Analysis System is an automated microchip flow chamber system that is used for the quantitative analysis of clot [...] Read more.

Background. Today there are many devices that can be used to study blood clotting disorders by identifying abnormalities in blood platelets. The Total Thrombus Formation Analysis System is an automated microchip flow chamber system that is used for the quantitative analysis of clot formation under blood flow conditions. For several years, researchers have been using a tool to analyse various clinical situations of patients to identify the properties and biochemical processes occurring within platelets and their microenvironment. Methods. An investigation of recent published literature was conducted based on PRISMA. This review includes 52 science papers directly related to the use of the Total Clot Formation Analysis System in relation to bleeding, surgery, platelet function assessment, anticoagulation monitoring, von Willebrand factor and others. Conclusion. Most available studies indicate that The Total Thrombus Formation Analysis System may be useful in diagnostic issues, with devices used to monitor therapy or as a significant tool for predicting bleeding events. However, T-TAS not that has the potential for diagnostic indications, but allows the direct observation of the flow and the interactions between blood cells, including the intensity and dynamics of clot formation. The device is expected to be of significant value for basic research to observe the interactions and changes within platelets and their microenvironment. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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14 pages, 1703 KiB

Open AccessReview

Platelet-Derived Extracellular Vesicles for Regenerative Medicine

by Miquel Antich-Rosselló, Maria Antònia Forteza-Genestra, Marta Monjo and Joana M. Ramis

Int. J. Mol. Sci. 2021, 22(16), 8580; https://doi.org/10.3390/ijms22168580 - 10 Aug 2021

Cited by 43 | Viewed by 6164

Abstract

Extracellular vesicles (EVs) present a great potential for the development of new treatments in the biomedical field. To be used as therapeutics, many different sources have been used for EVs obtention, while only a few studies have addressed the use of platelet-derived EVs [...] Read more.

Extracellular vesicles (EVs) present a great potential for the development of new treatments in the biomedical field. To be used as therapeutics, many different sources have been used for EVs obtention, while only a few studies have addressed the use of platelet-derived EVs (pEVs). In fact, pEVs have been shown to intervene in different healing responses, thus some studies have evaluated their regenerative capability in wound healing or hemorrhagic shock. Even more, pEVs have proven to induce cellular differentiation, enhancing musculoskeletal or neural regeneration. However, the obtention and characterization of pEVs is widely heterogeneous and differs from the recommendations of the International Society for Extracellular Vesicles. Therefore, in this review, we aim to present the main advances in the therapeutical use of pEVs in the regenerative medicine field while highlighting the isolation and characterization steps followed. The main goal of this review is to portray the studies performed in order to enhance the translation of the pEVs research into feasible therapeutical applications. Full article

(This article belongs to the Special Issue Recent Advances in Biological Functions of Platelet)

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