Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation
Mesenchymal stem cells (MSCs) have emerged as a potent therapeutic tool for the treatment of a number of pathologies, including immune pathologies. However, unwelcome effects of MSCs on blood coagulation have been reported, motivating us to explore the thrombotic properties of human MSCs from the um...
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MDPI AG
2019-03-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/8/3/258 |
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| author | Denis N. Silachev Kirill V. Goryunov Margarita A. Shpilyuk Olga S. Beznoschenko Natalya Y. Morozova Elizaveta E. Kraevaya Vasily A. Popkov Irina B. Pevzner Ljubava D. Zorova Ekaterina A. Evtushenko Natalia L. Starodubtseva Alexey S. Kononikhin Anna E. Bugrova Evgeniy G. Evtushenko Egor Y. Plotnikov Dmitry B. Zorov Gennady T. Sukhikh |
| author_facet | Denis N. Silachev Kirill V. Goryunov Margarita A. Shpilyuk Olga S. Beznoschenko Natalya Y. Morozova Elizaveta E. Kraevaya Vasily A. Popkov Irina B. Pevzner Ljubava D. Zorova Ekaterina A. Evtushenko Natalia L. Starodubtseva Alexey S. Kononikhin Anna E. Bugrova Evgeniy G. Evtushenko Egor Y. Plotnikov Dmitry B. Zorov Gennady T. Sukhikh |
| author_sort | Denis N. Silachev |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) have emerged as a potent therapeutic tool for the treatment of a number of pathologies, including immune pathologies. However, unwelcome effects of MSCs on blood coagulation have been reported, motivating us to explore the thrombotic properties of human MSCs from the umbilical cord. We revealed strong procoagulant effects of MSCs on human blood and platelet-free plasma using rotational thromboelastometry and thrombodynamic tests. A similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EVs). To offer approaches to avoid unwanted effects, we studied the impact of a heparin supplement on MSC procoagulative properties. However, MSCs still retained procoagulant activity toward blood from children receiving a therapeutic dose of unfractionated heparin. An analysis of the mechanisms responsible for the procoagulant effect of MSCs/EVs revealed the presence of tissue factor and other proteins involved in coagulation-associated pathways. Also, we found that some MSCs and EVs were positive for annexin V, which implies the presence of phosphatidylserine on their surfaces, which can potentiate clot formation. Thus, we revealed procoagulant activity of MSCs/EVs associated with the presence of phosphatidylserine and tissue factor, which requires further analysis to avoid adverse effects of MSC therapy in patients with a risk of thrombosis. |
| first_indexed | 2024-03-12T07:43:13Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:43:13Z |
| publishDate | 2019-03-01 |
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| series | Cells |
| spelling | doaj.art-1113a63d6fa84de1824b2f75c67337cd2023-09-02T21:09:41ZengMDPI AGCells2073-44092019-03-018325810.3390/cells8030258cells8030258Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood CoagulationDenis N. Silachev0Kirill V. Goryunov1Margarita A. Shpilyuk2Olga S. Beznoschenko3Natalya Y. Morozova4Elizaveta E. Kraevaya5Vasily A. Popkov6Irina B. Pevzner7Ljubava D. Zorova8Ekaterina A. Evtushenko9Natalia L. Starodubtseva10Alexey S. Kononikhin11Anna E. Bugrova12Evgeniy G. Evtushenko13Egor Y. Plotnikov14Dmitry B. Zorov15Gennady T. Sukhikh16V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaFaculty of Biology, Lomonosov Moscow State University, Moscow 119234, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaFaculty of Chemistry, Lomonosov Moscow State University, Moscow 119992, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, RussiaMesenchymal stem cells (MSCs) have emerged as a potent therapeutic tool for the treatment of a number of pathologies, including immune pathologies. However, unwelcome effects of MSCs on blood coagulation have been reported, motivating us to explore the thrombotic properties of human MSCs from the umbilical cord. We revealed strong procoagulant effects of MSCs on human blood and platelet-free plasma using rotational thromboelastometry and thrombodynamic tests. A similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EVs). To offer approaches to avoid unwanted effects, we studied the impact of a heparin supplement on MSC procoagulative properties. However, MSCs still retained procoagulant activity toward blood from children receiving a therapeutic dose of unfractionated heparin. An analysis of the mechanisms responsible for the procoagulant effect of MSCs/EVs revealed the presence of tissue factor and other proteins involved in coagulation-associated pathways. Also, we found that some MSCs and EVs were positive for annexin V, which implies the presence of phosphatidylserine on their surfaces, which can potentiate clot formation. Thus, we revealed procoagulant activity of MSCs/EVs associated with the presence of phosphatidylserine and tissue factor, which requires further analysis to avoid adverse effects of MSC therapy in patients with a risk of thrombosis.http://www.mdpi.com/2073-4409/8/3/258mesenchymal stem cellsextracellular vesiclesthrombosisheparinprocoagulant proteins |
| spellingShingle | Denis N. Silachev Kirill V. Goryunov Margarita A. Shpilyuk Olga S. Beznoschenko Natalya Y. Morozova Elizaveta E. Kraevaya Vasily A. Popkov Irina B. Pevzner Ljubava D. Zorova Ekaterina A. Evtushenko Natalia L. Starodubtseva Alexey S. Kononikhin Anna E. Bugrova Evgeniy G. Evtushenko Egor Y. Plotnikov Dmitry B. Zorov Gennady T. Sukhikh Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation Cells mesenchymal stem cells extracellular vesicles thrombosis heparin procoagulant proteins |
| title | Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation |
| title_full | Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation |
| title_fullStr | Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation |
| title_full_unstemmed | Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation |
| title_short | Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation |
| title_sort | effect of mscs and msc derived extracellular vesicles on human blood coagulation |
| topic | mesenchymal stem cells extracellular vesicles thrombosis heparin procoagulant proteins |
| url | http://www.mdpi.com/2073-4409/8/3/258 |
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