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3. Microlyse: a thrombolytic agent that targets VWF for clearance of microvascular thrombosis

Author

de Maat, Steven, Clark, Chantal C., Barendrecht, Arjan D., Smits, Simone, van Kleef, Nadine D., El Otmani, Hinde, Waning, Manon, van Moorsel, Marc, Szardenings, Michael, Delaroque, Nicolas, Vercruysse, Kristof, Urbanus, Rolf T., Sebastian, Silvie, Lenting, Peter J., Hagemeyer, Christoph, Renné, Thomas, Vanhoorelbeke, Karen, Tersteeg, Claudia, and Maas, Coen

Published
2022
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4. Influenza-induced thrombocytopenia is dependent on the subtype and sialoglycan receptor and increases with virus pathogenicity

Author

Jansen, A. J. Gerard, Spaan, Thom, Low, Hui Zhi, Di Iorio, Daniele, van den Brand, Judith, Tieke, Malte, Barendrecht, Arjan, Rohn, Kerstin, van Amerongen, Geert, Stittelaar, Koert, Baumgärtner, Wolfgang, Osterhaus, Albert, Kuiken, Thijs, Boons, Geert-Jan, Huskens, Jurriaan, Boes, Marianne, Maas, Coen, and van der Vries, Erhard

Published
2020
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8. Metallated phthalocyanines and their hydrophilic derivatives for multi-targeted oncological photodynamic therapy

Author

Developmental Biology, Afd Pharmaceutics, Sub Membrane Biochemistry & Biophysics, Sub Developmental Biology, Pharmaceutics, Membrane Biochemistry and Biophysics, Dias, Lionel Mendes, De keijzer, Mark J., Ernst, Daniël, Sharifi, Farangis, De klerk, Daniel J., Kleijn, Tony G., Desclos, Emilie, Kochan, Jakub A., De haan, Lianne R., Franchi, Leonardo P., Van wijk, Albert C., Scutigliani, Enzo M., Fens, Marcel H., Barendrecht, Arjan D., Cavaco, José E.b., Huang, Xuan, Xu, Ying, Pan, Weiwei, Den broeder, Marjo J., Bogerd, Jan, Schulz, Rüdiger W., Castricum, Kitty C., Thijssen, Victor L., Cheng, Shuqun, Ding, Baoyue, Krawczyk, Przemek M., Heger, Michal, Developmental Biology, Afd Pharmaceutics, Sub Membrane Biochemistry & Biophysics, Sub Developmental Biology, Pharmaceutics, Membrane Biochemistry and Biophysics, Dias, Lionel Mendes, De keijzer, Mark J., Ernst, Daniël, Sharifi, Farangis, De klerk, Daniel J., Kleijn, Tony G., Desclos, Emilie, Kochan, Jakub A., De haan, Lianne R., Franchi, Leonardo P., Van wijk, Albert C., Scutigliani, Enzo M., Fens, Marcel H., Barendrecht, Arjan D., Cavaco, José E.b., Huang, Xuan, Xu, Ying, Pan, Weiwei, Den broeder, Marjo J., Bogerd, Jan, Schulz, Rüdiger W., Castricum, Kitty C., Thijssen, Victor L., Cheng, Shuqun, Ding, Baoyue, Krawczyk, Przemek M., and Heger, Michal

Published
2022

9. Metallated phthalocyanines and their hydrophilic derivatives for multi-targeted oncological photodynamic therapy

Author

Dias, Lionel Mendes, de Keijzer, Mark J., Ernst, Daniël, Sharifi, Farangis, de Klerk, Daniel J., Kleijn, Tony G., Desclos, Emilie, Kochan, Jakub A., de Haan, Lianne R., Franchi, Leonardo P., van Wijk, Albert C., Scutigliani, Enzo M., Fens, Marcel H., Barendrecht, Arjan D., Cavaco, José E.B., Huang, Xuan, Xu, Ying, Pan, Weiwei, den Broeder, Marjo J., Bogerd, Jan, Schulz, Rüdiger W., Castricum, Kitty C., Thijssen, Victor L., Cheng, Shuqun, Ding, Baoyue, Krawczyk, Przemek M., Heger, Michal, Dias, Lionel Mendes, de Keijzer, Mark J., Ernst, Daniël, Sharifi, Farangis, de Klerk, Daniel J., Kleijn, Tony G., Desclos, Emilie, Kochan, Jakub A., de Haan, Lianne R., Franchi, Leonardo P., van Wijk, Albert C., Scutigliani, Enzo M., Fens, Marcel H., Barendrecht, Arjan D., Cavaco, José E.B., Huang, Xuan, Xu, Ying, Pan, Weiwei, den Broeder, Marjo J., Bogerd, Jan, Schulz, Rüdiger W., Castricum, Kitty C., Thijssen, Victor L., Cheng, Shuqun, Ding, Baoyue, Krawczyk, Przemek M., and Heger, Michal

Abstract

Background and aim: A photosensitizer (PS) delivery and comprehensive tumor targeting platform was developed that is centered on the photosensitization of key pharmacological targets in solid tumors (cancer cells, tumor vascular endothelium, and cellular and non-cellular components of the tumor microenvironment) before photodynamic therapy (PDT). Interstitially targeted liposomes (ITLs) encapsulating zinc phthalocyanine (ZnPC) and aluminum phthalocyanine (AlPC) were formulated for passive targeting of the tumor microenvironment. In previous work it was established that the PEGylated ITLs were taken up by cultured cholangiocarcinoma cells. The aim of this study was to verify previous results in cancer cells and to determine whether the ITLs can also be used to photosensitize cells in the tumor microenvironment and vasculature. Following positive results, rudimentary in vitro and in vivo experiments were performed with ZnPC-ITLs and AlPC-ITLs as well as their water-soluble tetrasulfonated derivatives (ZnPCS4 and AlPCS4) to assemble a research dossier and bring this platform closer to clinical transition. Methods: Flow cytometry and confocal microscopy were employed to determine ITL uptake and PS distribution in cholangiocarcinoma (SK-ChA-1) cells, endothelial cells (HUVECs), fibroblasts (NIH-3T3), and macrophages (RAW 264.7). Uptake of ITLs by endothelial cells was verified under flow conditions in a flow chamber. Dark toxicity and PDT efficacy were determined by cell viability assays, while the mode of cell death and cell cycle arrest were assayed by flow cytometry. In vivo systemic toxicity was assessed in zebrafish and chicken embryos, whereas skin phototoxicity was determined in BALB/c nude mice. A PDT efficacy pilot was conducted in BALB/c nude mice bearing human triple-negative breast cancer (MDA-MB-231) xenografts. Results: The key findings were that (1) photodynamically active PSs (i.e., all except ZnPCS4) were able to effectively photosensitize cancer cell

Published
2022

10. VhH anti-thrombomodulin clone 1 inhibits TAFI activation and enhances fibrinolysis in human whole blood under flow

Author

CDL Nanomedicine, Poli Van Creveldkliniek Medisch, Centraal Diagnostisch Laboratorium, CDL Contact activatie, Circulatory Health, CDL Research analisten, Cancer, CDL Cluster Onderzoek en Onderwijs, van Moorsel, Marc V A, Poolen, Geke, Koekman, Cornelis A, Verhoef, Sandra, de Maat, Steven, Barendrecht, Arjan, van Kleef, Nadine D, Meijers, Joost C M, Schiffelers, Raymond, Maas, Coen, Urbanus, Rolf T, CDL Nanomedicine, Poli Van Creveldkliniek Medisch, Centraal Diagnostisch Laboratorium, CDL Contact activatie, Circulatory Health, CDL Research analisten, Cancer, CDL Cluster Onderzoek en Onderwijs, van Moorsel, Marc V A, Poolen, Geke, Koekman, Cornelis A, Verhoef, Sandra, de Maat, Steven, Barendrecht, Arjan, van Kleef, Nadine D, Meijers, Joost C M, Schiffelers, Raymond, Maas, Coen, and Urbanus, Rolf T

Published
2022

11. Microlyse; a thrombolytic agent that targets VWF for clearance of microvascular thrombosis

Author

CDL Contact activatie, Circulatory Health, CDL Research analisten, CDL Nanomedicine, Poli Van Creveldkliniek Medisch, CDL Staf Research, de Maat, Steven, Clark, Chantal, Barendrecht, Arjan D, Smits, Simone, van Kleef, Nadine D, El Otmani, Hinde, Waning, Manon, van Moorsel, Marc Vincent Adriaan, Szardenings, Michael, Delaroque, Nicolas, Vercruysse, Kristof, Urbanus, Rolf T, Sebastian, Silvie, Lenting, Peter J, Hagemeyer, Christoph Eugen, Renné, Thomas, Vanhoorelbeke, Karen, Tersteeg, Claudia, Maas, Coen, CDL Contact activatie, Circulatory Health, CDL Research analisten, CDL Nanomedicine, Poli Van Creveldkliniek Medisch, CDL Staf Research, de Maat, Steven, Clark, Chantal, Barendrecht, Arjan D, Smits, Simone, van Kleef, Nadine D, El Otmani, Hinde, Waning, Manon, van Moorsel, Marc Vincent Adriaan, Szardenings, Michael, Delaroque, Nicolas, Vercruysse, Kristof, Urbanus, Rolf T, Sebastian, Silvie, Lenting, Peter J, Hagemeyer, Christoph Eugen, Renné, Thomas, Vanhoorelbeke, Karen, Tersteeg, Claudia, and Maas, Coen

Published
2022

12. Targeted SERPIN (TaSER): a dual-action antithrombotic agent that targets platelets for SERPIN delivery

Author

CDL Contact activatie, CDL Research analisten, Poli Van Creveldkliniek Medisch, CDL Staf Research, Circulatory Health, Sanrattana, Wariya, Smits, Simone, Barendrecht, Arjan D, van Kleef, Nadine D, El Otmani, Hinde, Zivkovic, Minka, Roest, Mark, Renné, Thomas, Clark, Chantal C, de Maat, Steven, Maas, Coen, CDL Contact activatie, CDL Research analisten, Poli Van Creveldkliniek Medisch, CDL Staf Research, Circulatory Health, Sanrattana, Wariya, Smits, Simone, Barendrecht, Arjan D, van Kleef, Nadine D, El Otmani, Hinde, Zivkovic, Minka, Roest, Mark, Renné, Thomas, Clark, Chantal C, de Maat, Steven, and Maas, Coen

Published
2022

13. An increase in CD62L dim neutrophils precedes the development of pulmonary embolisms in COVID‐19 patients

Author

Spijkerman, Roy, Jorritsma, Nikita K. N., Bongers, Suzanne H., Bindels, Bas J. J., Jukema, Bernard N., Hesselink, Lillian, Hietbrink, Falco, Leenen, Luke P. H., Goor, Harriët M. R., Vrisekoop, Nienke, Kaasjager, Karin A. H., Koenderman, Leo, Stiphout, Feike, Nijdam, Thomas M. P., van de Ven, Nils L. M., Verhaegh, Remi, Spanjaard, Judith S., Verboeket, Benjamin W., Laane, Duco, van Wessem, Karlijn, van spengler, Daan E. J., Buitenwerf, Wiebe, Giustarini, Giulio, Mulder, Eva, Heijerman, Harry, Zabaleta, Amely Daza, van den bos, Frederique, Rademaker, Emma, Varkila, Meri R. J., de Mul, Nikki, Cremer, Olaf L., Slooter, Arjen, Delemarre, Eveline M., Nierkens, Stefan, Limper, Maarten, van Wijk, Femke, Pandit, Aridaman, Leavis, Helen, Clark, Chantal C., Barendrecht, Arjan D., Seinen, Cor W., Drost‐Verhoef, Sandra, Smits, Simone, Parr, Naomi M. J., Sebastian, Sylvie A. E., Koekman, Arnold C., van Wesel, Annet C., van der Vries, Erhard, Maas, Coen, de Maat, Steven, Haitjema, Saskia, and Hoefer, Imo E.

Subjects
Male, 0301 basic medicine, pulmonary embolism, Neutrophils, Receptor expression, SARS‐CoV‐2, Neutrophil Activation, law.invention, Cohort Studies, 0302 clinical medicine, Immunophenotyping, law, L‐selectin, L-Selectin, biology, Incidence (epidemiology), Regular Article, General Medicine, Middle Aged, Prognosis, Thrombosis, Intensive care unit, Pulmonary embolism, Intensive Care Units, Female, L-selectin, Disease Susceptibility, medicine.medical_specialty, Intensive Care Unit, Immunology, CD16, 03 medical and health sciences, COVID‐19, Internal medicine, medicine, CD62L, Humans, Aged, SARS-CoV-2, business.industry, COVID-19, medicine.disease, 030104 developmental biology, biology.protein, business, Biomarkers, Regular Articles, 030215 immunology
Abstract

Objectives A high incidence of pulmonary embolism (PE) is reported in patients with critical coronavirus disease 2019 (COVID‐19). Neutrophils may contribute to this through a process referred to as immunothrombosis. The aim of this study was to investigate the occurrence of neutrophil subpopulations in blood preceding the development of COVID‐19 associated PE. Methods We studied COVID‐19 patients admitted to the ICU of our tertiary hospital between 19‐03‐2020 and 17‐05‐2020. Point‐of‐care fully automated flow cytometry was performed prior to ICU admission, measuring the neutrophil activation/maturation markers CD10, CD11b, CD16 and CD62L. Neutrophil receptor expression was compared between patients who did or did not develop PE (as diagnosed on CT angiography) during or after their ICU stay. Results Among 25 eligible ICU patients, 22 subjects were included for analysis, of whom nine developed PE. The median (IQR) time between neutrophil phenotyping and PE occurrence was 9 (7‐12) days. A significant increase in the immune‐suppressive neutrophil phenotype CD16bright/CD62Ldim was observed on the day of ICU admission (P = 0.014) in patients developing PE compared to patients who did not. Conclusion The increase in this neutrophil phenotype indicates that the increased number of CD16bright/CD62Ldim neutrophils might be used as prognostic marker to predict those patients that will develop PE in critical COVID‐19 patients.

Published
2021

15. Thrombotic Events in COVID-19 Are Associated With a Lower Use of Prophylactic Anticoagulation Before Hospitalization and Followed by Decreases in Platelet Reactivity

Author

Clark, Chantal C., primary, Jukema, Bernard N., additional, Barendrecht, Arjan D., additional, Spanjaard, Judith S., additional, Jorritsma, Nikita K. N., additional, Smits, Simone, additional, de Maat, Steven, additional, Seinen, Cor W., additional, Verhoef, Sandra, additional, Parr, Naomi M. J., additional, Sebastian, Silvie A. E., additional, Koekman, Arnold C., additional, van Wesel, Annet C. W., additional, van Goor, Harriet M. R., additional, Spijkerman, Roy, additional, Bongers, Suzanne H., additional, van der Vries, Erhard, additional, Nierkens, Stefan, additional, Boes, Marianne, additional, Koenderman, Leo, additional, Kaasjager, Karin A. H., additional, and Maas, Coen, additional

Published
2021
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16. Normoxic Tumour Extracellular Vesicles Modulate the Response of Hypoxic Cancer and Stromal Cells to Doxorubicin In Vitro

Author

Patras, Laura, Fens, Marcel H A M, Vader, Pieter, Barendrecht, Arjan, Sesarman, Alina, Banciu, Manuela, Schiffelers, Raymond, Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, and Pharmaceutics

Subjects
Stromal cell, Colorectal cancer, normoxia, bcl-X Protein, doxorubicin, Catalysis, Article, Inorganic Chemistry, lcsh:Chemistry, Mice, Cell Line, Tumor, medicine, Animals, Cytotoxic T cell, Doxorubicin, Viability assay, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Antibiotics, Antineoplastic, Chemistry, hypoxia, Organic Chemistry, General Medicine, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, In vitro, Computer Science Applications, macrophages, Crosstalk (biology), RAW 264.7 Cells, lcsh:Biology (General), lcsh:QD1-999, colon cancer, Drug Resistance, Neoplasm, Colonic Neoplasms, Cancer cell, Cancer research, Tumor Hypoxia, Stromal Cells, extracellular vesicles, medicine.drug
Abstract

Extracellular vesicles (EV) secreted in the tumour microenvironment (TME) are emerging as major antagonists of anticancer therapies by orchestrating the therapeutic outcome through altering the behaviour of recipient cells. Recent evidence suggested that chemotherapeutic drugs could be responsible for the EV-mediated tumour&ndash, stroma crosstalk associated with cancer cell drug resistance. Here, we investigated the capacity of tumour EV (TEV) secreted by normoxic and hypoxic (1% oxygen) C26 cancer cells after doxorubicin (DOX) treatment to alter the response of na&iuml, ve C26 cells and RAW 264.7 macrophages to DOX. We observed that C26 cells were less responsive to DOX treatment under normoxia compared to hypoxia, and a minimally cytotoxic DOX concentration that mounted distinct effects on cell viability was selected for TEV harvesting. Homotypic and heterotypic pretreatment of na&iuml, ve hypoxic cancer and macrophage-like cells with normoxic DOX-elicited TEV rendered these cells slightly less responsive to DOX treatment. The observed effects were associated with strong hypoxia-inducible factor 1-alpha (HIF-1&alpha, ) induction and B-cell lymphoma&ndash, extra-large anti-apoptotic protein (Bcl-xL)-mediated anti-apoptotic response in normoxic DOX-treated TEV donor cells, being also tightly connected to the DOX-TEV-mediated HIF-1&alpha, induction, as well as Bcl-xL levels increasing in recipient cells. Altogether, our results could open new perspectives for investigating the role of chemotherapy-elicited TEV in the colorectal cancer TME and their modulatory actions on promoting drug resistance.

Published
2020

17. Endothelial Cell Targeting by cRGD-Functionalized Polymeric Nanoparticles under Static and Flow Conditions

Author

Martínez-Jothar, Lucía, Barendrecht, Arjan D, de Graaff, Anko M, Oliveira, Sabrina, van Nostrum, Cornelus F, Schiffelers, Raymond M, Hennink, Wim E, Fens, Marcel H A M, Afd Pharmaceutics, Sub Cell Biology, Pharmaceutics, Celbiologie, Afd Pharmaceutics, Sub Cell Biology, Pharmaceutics, and Celbiologie

Subjects
Endothelium, Angiogenesis, physiological flow, General Chemical Engineering, 02 engineering and technology, Umbilical vein, Article, Flow cytometry, lcsh:Chemistry, 03 medical and health sciences, chemistry.chemical_compound, In vivo, medicine, General Materials Science, targeting, 030304 developmental biology, 0303 health sciences, RGD, medicine.diagnostic_test, Chemistry, PLGA, 021001 nanoscience & nanotechnology, endothelial cells, Endothelial stem cell, medicine.anatomical_structure, lcsh:QD1-999, Biophysics, nanoparticles, Nanocarriers, 0210 nano-technology
Abstract

Since &alpha, v&beta, 3 integrin is a key component of angiogenesis in health and disease, Arg-Gly-Asp (RGD) peptide-functionalized nanocarriers have been investigated as vehicles for targeted delivery of drugs to the &alpha, 3 integrin-overexpressing neovasculature of tumors. In this work, PEGylated nanoparticles (NPs) based on poly(lactic-co-glycolic acid) (PLGA) functionalized with cyclic-RGD (cRGD), were evaluated as nanocarriers for the targeting of angiogenic endothelium. For this purpose, NPs (~300 nm) functionalized with cRGD with different surface densities were prepared by maleimide-thiol chemistry and their interactions with human umbilical vein endothelial cells (HUVECs) were evaluated under different conditions using flow cytometry and microscopy. The cell association of cRGD-NPs under static conditions was time-, concentration- and cRGD density-dependent. The interactions between HUVECs and cRGD-NPs dispersed in cell culture medium under flow conditions were also time- and cRGD density-dependent. When washed red blood cells (RBCs) were added to the medium, a 3 to 8-fold increase in NPs association to HUVECs was observed. Moreover, experiments conducted under flow in the presence of RBC at physiologic hematocrit and shear rate, are a step forward in the prediction of in vivo cell&ndash, particle association. This approach has the potential to assist development and high-throughput screening of new endothelium-targeted nanocarriers.

Published
2020

19. Influenza-induced thrombocytopenia is dependent on the subtype and sialoglycan receptor and increases with virus pathogenicity

Author

VPDC pathologie, dPB I&I, dPB CR, dI&I I&I-1, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, dIRAS RA-1, Jansen, A J Gerard, Spaan, Thom, Low, Hui Zhi, Di Iorio, Daniele, van den Brand, Judith, Tieke, Malte, Barendrecht, Arjan, Rohn, Kerstin, van Amerongen, Geert, Stittelaar, Koert, Baumgärtner, Wolfgang, Osterhaus, Albert, Kuiken, Thijs, Boons, Geert-Jan, Huskens, Jurriaan, Boes, Marianne, Maas, Coen, van der Vries, Erhard, VPDC pathologie, dPB I&I, dPB CR, dI&I I&I-1, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, dIRAS RA-1, Jansen, A J Gerard, Spaan, Thom, Low, Hui Zhi, Di Iorio, Daniele, van den Brand, Judith, Tieke, Malte, Barendrecht, Arjan, Rohn, Kerstin, van Amerongen, Geert, Stittelaar, Koert, Baumgärtner, Wolfgang, Osterhaus, Albert, Kuiken, Thijs, Boons, Geert-Jan, Huskens, Jurriaan, Boes, Marianne, Maas, Coen, and van der Vries, Erhard

Published
2020

20. Endothelial Cell Targeting by cRGD-Functionalized Polymeric Nanoparticles under Static and Flow Conditions

Author

Afd Pharmaceutics, Sub Cell Biology, Pharmaceutics, Celbiologie, Martínez-Jothar, Lucía, Barendrecht, Arjan D, de Graaff, Anko M, Oliveira, Sabrina, van Nostrum, Cornelus F, Schiffelers, Raymond M, Hennink, Wim E, Fens, Marcel H A M, Afd Pharmaceutics, Sub Cell Biology, Pharmaceutics, Celbiologie, Martínez-Jothar, Lucía, Barendrecht, Arjan D, de Graaff, Anko M, Oliveira, Sabrina, van Nostrum, Cornelus F, Schiffelers, Raymond M, Hennink, Wim E, and Fens, Marcel H A M

Published
2020

21. Endothelial cell targeting by crgd-functionalized polymeric nanoparticles under static and flow conditions

Author

CDL Research analisten, CDL Cluster Onderzoek en Onderwijs, Circulatory Health, Cancer, CDL Nanomedicine, Martínez-Jothar, Lucía, Barendrecht, Arjan D., de Graaff, Anko M., Oliveira, Sabrina, van Nostrum, Cornelus F., Schiffelers, Raymond M., Hennink, Wim E., Fens, Marcel H.A.M., CDL Research analisten, CDL Cluster Onderzoek en Onderwijs, Circulatory Health, Cancer, CDL Nanomedicine, Martínez-Jothar, Lucía, Barendrecht, Arjan D., de Graaff, Anko M., Oliveira, Sabrina, van Nostrum, Cornelus F., Schiffelers, Raymond M., Hennink, Wim E., and Fens, Marcel H.A.M.

Published
2020

22. Normoxic Tumour Extracellular Vesicles Modulate the Response of Hypoxic Cancer and Stromal Cells to Doxorubicin In Vitro

Author

CDL Nanomedicine, Cancer, Circulatory Health, CDL Research analisten, CDL Cluster Onderzoek en Onderwijs, Patras, Laura, Fens, Marcel H A M, Vader, Pieter, Barendrecht, Arjan, Sesarman, Alina, Banciu, Manuela, Schiffelers, Raymond, CDL Nanomedicine, Cancer, Circulatory Health, CDL Research analisten, CDL Cluster Onderzoek en Onderwijs, Patras, Laura, Fens, Marcel H A M, Vader, Pieter, Barendrecht, Arjan, Sesarman, Alina, Banciu, Manuela, and Schiffelers, Raymond

Published
2020

25. Heparin Forms Polymers with Cell-free DNA Which Elongate Under Shear in Flowing Blood

Author

MS Nefrologie, CDL Research analisten, CDL Contact activatie, Poli Van Creveldkliniek Medisch, Circulatory Health, CTI Leusen, CDL Staf Research, de Vries, Joost C, Barendrecht, Arjan D, Clark, Chantal C, Urbanus, Rolf T, Boross, Peter, de Maat, Steven, Maas, Coen, MS Nefrologie, CDL Research analisten, CDL Contact activatie, Poli Van Creveldkliniek Medisch, Circulatory Health, CTI Leusen, CDL Staf Research, de Vries, Joost C, Barendrecht, Arjan D, Clark, Chantal C, Urbanus, Rolf T, Boross, Peter, de Maat, Steven, and Maas, Coen

Published
2019

26. Live-cell Imaging of Platelet Degranulation and Secretion Under Flow

Author

Barendrecht, Arjan D, Verhoef, Johan J F, Pignatelli, Silvia, Pasterkamp, Gerard, Heijnen, Harry F G, Maas, Coen, Pharmaceutics, and Pharmaceutics

Subjects
0301 basic medicine, Platelets, Blood Platelets, General Chemical Engineering, Neuroscience(all), Biochemistry, Fluorescence, General Biochemistry, Genetics and Molecular Biology, law.invention, 03 medical and health sciences, Platelet Adhesiveness, Platelet degranulation, Confocal microscopy, law, Live cell imaging, Platelet adhesiveness, Immunology and Microbiology(all), Microscopy, Fluorescence microscope, Journal Article, Humans, Video-Audio Media, Platelet, Secretion, Hemostasis, General Immunology and Microbiology, Chemistry, Biochemistry, Genetics and Molecular Biology(all), General Neuroscience, Thrombosis, Cell biology, Cellular Biology, 030104 developmental biology, Microscopy, Fluorescence, Issue 125, Biophysics, Adhesion, Chemical Engineering(all), Genetics and Molecular Biology(all)
Abstract

Blood platelets are essential players in hemostasis, the formation of thrombi to seal vascular breaches. They are also involved in thrombosis, the formation of thrombi that occlude the vasculature and injure organs, with life-threatening consequences. This motivates scientific research on platelet function and the development of methods to track cell-biological processes as they occur under flow conditions. A variety of flow models are available for the study of platelet adhesion and aggregation, two key phenomena in platelet biology. This work describes a method to study real-time platelet degranulation under flow during activation. The method makes use of a flow chamber coupled to a syringe-pump setup that is placed under a wide-field, inverted, LED-based fluorescence microscope. The setup described here allows for the simultaneous excitation of multiple fluorophores that are delivered by fluorescently labeled antibodies or fluorescent dyes. After live-cell imaging experiments, the cover glasses can be further processed and analyzed using static microscopy (i.e., confocal microscopy or scanning electron microscopy).

Published
2017

29. Live-cell Imaging of Platelet Degranulation and Secretion Under Flow

Author

Pharmaceutics, Barendrecht, Arjan D, Verhoef, Johan J F, Pignatelli, Silvia, Pasterkamp, Gerard, Heijnen, Harry F G, Maas, Coen, Pharmaceutics, Barendrecht, Arjan D, Verhoef, Johan J F, Pignatelli, Silvia, Pasterkamp, Gerard, Heijnen, Harry F G, and Maas, Coen

Published
2017

30. Polyphosphate nanoparticles on the platelet surface trigger contact system activation

Author

Afd Pharmaceutics, Pharmaceutics, Verhoef, Johan J F, Barendrecht, Arjan D, Nickel, Katrin F, Dijkxhoorn, Kim, Kenne, Ellinor, Labberton, Linda, McCarty, Owen J T, Schiffelers, Raymond, Heijnen, Harry F G, Hendrickx, Antoni P A, Schellekens, Huub, Fens, Marcel H, de Maat, Steven, Renné, Thomas, Maas, Coen, Afd Pharmaceutics, Pharmaceutics, Verhoef, Johan J F, Barendrecht, Arjan D, Nickel, Katrin F, Dijkxhoorn, Kim, Kenne, Ellinor, Labberton, Linda, McCarty, Owen J T, Schiffelers, Raymond, Heijnen, Harry F G, Hendrickx, Antoni P A, Schellekens, Huub, Fens, Marcel H, de Maat, Steven, Renné, Thomas, and Maas, Coen

Published
2017

31. Polyphosphate nanoparticles on the platelet surface trigger contact system activation

Author

Verhoef, Johan J F, Barendrecht, Arjan D, Nickel, Katrin F, Dijkxhoorn, Kim, Kenne, Ellinor, Labberton, Linda, McCarty, Owen J T, Schiffelers, Raymond, Heijnen, Harry F, Hendrickx, Antoni P, Schellekens, Huub, Fens, Marcel H, de Maat, Steven, Renné, Thomas, Maas, Coen, Verhoef, Johan J F, Barendrecht, Arjan D, Nickel, Katrin F, Dijkxhoorn, Kim, Kenne, Ellinor, Labberton, Linda, McCarty, Owen J T, Schiffelers, Raymond, Heijnen, Harry F, Hendrickx, Antoni P, Schellekens, Huub, Fens, Marcel H, de Maat, Steven, Renné, Thomas, and Maas, Coen

Published
2017

32. Live-cell imaging of platelet degranulation and secretion under flow

Author

CDL Pre-analyse Centraal, Centraal Diagnostisch Laboratorium, CDL Cluster Onderzoek en Onderwijs, CDL Staf Research, Circulatory Health, Barendrecht, Arjan D., Verhoef, Johan J F, Pignatelli, Silvia, Pasterkamp, Gerard, Heijnen, Harry F.G., Maas, Coen, CDL Pre-analyse Centraal, Centraal Diagnostisch Laboratorium, CDL Cluster Onderzoek en Onderwijs, CDL Staf Research, Circulatory Health, Barendrecht, Arjan D., Verhoef, Johan J F, Pignatelli, Silvia, Pasterkamp, Gerard, Heijnen, Harry F.G., and Maas, Coen

Published
2017

33. Polyphosphate nanoparticles on the platelet surface trigger contact system activation

Author

Centraal Diagnostisch Laboratorium, CDL Staf Research, Circulatory Health, MMB Research line 2, Infection & Immunity, CDL Nanomedicine, Cancer, CDL Contact activatie, Verhoef, Johan J F, Barendrecht, Arjan D, Nickel, Katrin F, Dijkxhoorn, Kim, Kenne, Ellinor, Labberton, Linda, McCarty, Owen J T, Schiffelers, Raymond, Heijnen, Harry F, Hendrickx, Antoni P, Schellekens, Huub, Fens, Marcel H, de Maat, Steven, Renné, Thomas, Maas, Coen, Centraal Diagnostisch Laboratorium, CDL Staf Research, Circulatory Health, MMB Research line 2, Infection & Immunity, CDL Nanomedicine, Cancer, CDL Contact activatie, Verhoef, Johan J F, Barendrecht, Arjan D, Nickel, Katrin F, Dijkxhoorn, Kim, Kenne, Ellinor, Labberton, Linda, McCarty, Owen J T, Schiffelers, Raymond, Heijnen, Harry F, Hendrickx, Antoni P, Schellekens, Huub, Fens, Marcel H, de Maat, Steven, Renné, Thomas, and Maas, Coen

Published
2017

34. Interaction of extracellular vesicles with endothelial cells under physiological flow conditions

Author

CDL Patiëntenzorg KC, Centraal Diagnostisch Laboratorium, UMC Utrecht, Circulatory Health, van Dommelen, Susan M., Fish, Margaret, Barendrecht, Arjan D, Schiffelers, Raymond M., Eniola-Adefeso, Omolola, Vader, Pieter, CDL Patiëntenzorg KC, Centraal Diagnostisch Laboratorium, UMC Utrecht, Circulatory Health, van Dommelen, Susan M., Fish, Margaret, Barendrecht, Arjan D, Schiffelers, Raymond M., Eniola-Adefeso, Omolola, and Vader, Pieter

Published
2017

35. Response to letter regarding article, 'plasmin cleavage of von willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy'

Author

Tersteeg, Claudia, de Maat, Steven, De Meyer, Simon F, Smeets, Michel W J, Barendrecht, Arjan D, Roest, Mark, Pasterkamp, Gerard, Fijnheer, Rob, Vanhoorelbeke, Karen, de Groot, Philip G, and Maas, Coen

Subjects
ADAM Proteins, Letter, Thrombotic Microangiopathies, Fibrinolysis, von Willebrand Factor, Comment, Animals, Humans, Fibrinolysin
Published
2015

36. Plasmin-Cleaved Von Willebrand Factor As a Biomarker for Microvascular Thrombosis

Author

El Otmani, Hinde, Frunt, Rowan, Smits, Simone, De Maat, Steven, Fijnheer, Rob, Barendrecht, Arjan, Lenting, Peter J, and Tersteeg, Claudia

Abstract

Von Willebrand factor (VWF) is an essential contributor to microvascular thrombosis. Physiological cleavage by ADAMTS13 limits its prothrombotic properties, explaining why ADAMTS13 deficiency leads to attacks of microthrombosis in patients with thrombotic thrombocytopenic purpura (TTP). We previously reported that plasminogen activation takes place during TTP attacks in these patients. Furthermore, stimulation of plasminogen activation attenuates pathogenesis in preclinical TTP models in vivo. This suggests that plasmin is an endogenous regulator of VWF thrombogenicity, in particular when ADAMTS13 falls short to prevent microvascular occlusions. VWF cleavage by plasmin is biochemically distinct from cleavage by ADAMTS13. We hypothesized that plasmin-cleaved VWF (cVWF) holds value as a biomarker of microvascular thrombosis. We developed a V HH-based bioassay that can distinguish cVWF from intact and ADAMTS13-cleaved VWF in plasma. We validate this assay by tracking cVWF release during degradation of microthombi in vitro. We demonstrate that endogenous cVWF formation takes place in TTP patients during acute attacks of thrombotic microangiopathy, but not in remission. Finally, we show that therapeutic plasminogen activation in a mouse model for TTP amplifies cVWF formation, which is accompanied by VWF clearance. Our combined findings indicate that cVWF is released from microthrombi in the context of microvascular occlusion.

Published
2023
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37. Response to letter regarding article, 'plasmin cleavage of von willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy'

Author

CDL Contact activatie, Circulatory Health, Centraal Diagnostisch Laboratorium, Onderzoek Vrouw Hart & Vaatziekten, CDL Cluster Onderzoek en Onderwijs, CDL Staf Research, Tersteeg, Claudia, de Maat, Steven, De Meyer, Simon F, Smeets, Michel W J, Barendrecht, Arjan D, Roest, Mark, Pasterkamp, Gerard, Fijnheer, Rob, Vanhoorelbeke, Karen, de Groot, Philip G, Maas, Coen, CDL Contact activatie, Circulatory Health, Centraal Diagnostisch Laboratorium, Onderzoek Vrouw Hart & Vaatziekten, CDL Cluster Onderzoek en Onderwijs, CDL Staf Research, Tersteeg, Claudia, de Maat, Steven, De Meyer, Simon F, Smeets, Michel W J, Barendrecht, Arjan D, Roest, Mark, Pasterkamp, Gerard, Fijnheer, Rob, Vanhoorelbeke, Karen, de Groot, Philip G, and Maas, Coen

Published
2015

38. Quantitative proteomics analysis reveals similar release profiles following specific PAR-1 or PAR-4 stimulation of platelets

Author

Sub Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy, van Holten, Thijs C, Bleijerveld, Onno B, Wijten, Patrick, de Groot, Philip G, Heck, Albert J R, Barendrecht, Arjan D, Merkx, Tesy H, Scholten, Arjen, Roest, Mark, Sub Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Molecular Pharmacy, van Holten, Thijs C, Bleijerveld, Onno B, Wijten, Patrick, de Groot, Philip G, Heck, Albert J R, Barendrecht, Arjan D, Merkx, Tesy H, Scholten, Arjen, and Roest, Mark

Published
2014

39. Plasmin Cleavage of von Willebrand Factor as an Emergency Bypass for ADAMTS13 Deficiency in Thrombotic Microangiopathy

Author

Tersteeg, Claudia, primary, de Maat, Steven, additional, De Meyer, Simon F., additional, Smeets, Michel W.J., additional, Barendrecht, Arjan D., additional, Roest, Mark, additional, Pasterkamp, Gerard, additional, Fijnheer, Rob, additional, Vanhoorelbeke, Karen, additional, de Groot, Philip. G., additional, and Maas, Coen, additional

Published
2014
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40. Response to letter regarding article, "plasmin cleavage of von willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy".

Author

Tersteeg C, de Maat S, De Meyer SF, Smeets MW, Barendrecht AD, Roest M, Pasterkamp G, Fijnheer R, Vanhoorelbeke K, de Groot PG, and Maas C

Subjects
Animals, Humans, ADAM Proteins metabolism, Fibrinolysin metabolism, Fibrinolysis physiology, Thrombotic Microangiopathies metabolism, von Willebrand Factor metabolism
Published
2015
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