Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation
Open accessAbstract
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.
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The risk of thrombosis from MSC-EVs cannot be ignored, especially for higher concentrations, due to the presence of procoagulant factors when systemically administered.
“Nevertheless, the risk of thrombosis cannot be ignored, especially for higher concentrations, due to the presence of procoagulant factors when systemically administered [241], [257].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [257]
The Results (§3.2; page unavailable) report dose-dependent activation of blood coagulation by MSC-derived EVs, and the Abstract identifies tissue factor and phosphatidylserine as associated procoagulant factors. These findings support concern about thrombosis, especially at higher concentrations, but the EV experiments added vesicles to blood or plasma in vitro; the paper does not establish thrombosis risk after systemic EV administration. (LLM, conf=0.86)
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Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine
Vizoso, F., Eiro, N., Cid, S., Schneider, J., & Perez-Fernandez, R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091852 · Cited by 1,363 · see citing works
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Research works printed but not linked: 71
- [1]Gao F. Chiu S.M. Motan D.A.L. Zhang Z. Chen L. Ji H.-L. Tse H.-F. Fu Q.-L. Lian Q. Mesenchymal stem cells and immunomodulation: Current status and future prospects Cell Death Dis. 2016 7 e2062 10.1038/cddis.2015.327 26794657 PMC4816164 · DOI
- [2]Horák J. Nalos L. Martínková V. Beneš J. Štengl M. Matějovič M. Mesenchymal Stem Cells in Sepsis and Associated Organ Dysfunction: A Promising Future or Blind Alley? Stem Cells Int. 2017 2017 7304121 10.1155/2017/7304121 29098010 PMC5618761 · DOI
- [3]Yu B. Zhang X. Li X. Exosomes derived from mesenchymal stem cells Int. J. Mol. Sci. 2014 15 4142 4157 10.3390/ijms15034142 24608926 PMC3975389 · DOI
- [4]Zhang B. Yin Y. Lai R.C. Lim S.K. Immunotherapeutic potential of extracellular vesicles Front. Immunol. 2014 5 518 10.3389/fimmu.2014.00518 25374570 PMC4205852 · DOI
- [5]Börger V. Bremer M. Ferrer-Tur R. Gockeln L. Stambouli O. Becic A. Giebel B. Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents Int. J. Mol. Sci. 2017 18 1450 10.3390/ijms18071450 PMC5535941 28684664 · DOI
- [7]Squillaro T. Peluso G. Galderisi U. Clinical Trials with Mesenchymal Stem Cells: An Update Cell Transplant. 2016 25 829 848 10.3727/096368915X689622 26423725 · DOI
- [8]Tatsumi K. Ohashi K. Matsubara Y. Kohori A. Ohno T. Kakidachi H. Horii A. Kanegae K. Utoh R. Iwata T. Tissue factor triggers procoagulation in transplanted mesenchymal stem cells leading to thromboembolism Biochem. Biophys. Res. Commun. 2013 431 203 209 10.1016/j.bbrc.2012.12.134 23313481 · DOI
- [9]Ozdemir E. Kansu E. Deep Vein Thrombosis Following Non-myeloablative Allogeneic Stem Cell Transplantation: Presentation of Three Cases and Literature Review Turk. J. Haematol. 2013 30 188 190 10.4274/Tjh.92499 24385784 PMC3878478 · DOI
- [10]Lim R. Malhotra A. Tan J. Chan S.T. Lau S. Zhu D. Mockler J.C. Wallace E.M. First-In-Human Administration of Allogeneic Amnion Cells in Premature Infants With Bronchopulmonary Dysplasia: A Safety Study Stem Cells Transl. Med. 2018 7 628 635 10.1002/sctm.18-0079 30078207 PMC6127230 · DOI
- [11]Jung J.W. Kwon M. Choi J.C. Shin J.W. Park I.W. Choi B.W. Kim J.Y. Familial occurrence of pulmonary embolism after intravenous, adipose tissue-derived stem cell therapy Yonsei Med. J. 2013 54 1293 1296 10.3349/ymj.2013.54.5.1293 23918585 PMC3743204 · DOI
- [12]Perlee D. van Vught L.A. Scicluna B.P. Maag A. Lutter R. Kemper E.M. van ’t Veer C. Punchard M.A. González J. Richard M.P. Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, Single-Blind, Parallel Group, Placebo Controlled Trial Stem Cells 2018 10.1002/stem.2891 30063804 · DOI
- [13]Stéphenne X. Vosters O. Najimi M. Beuneu C. Dung K.N. Wijns W. Goldman M. Sokal E.M. Tissue factor-dependent procoagulant activity of isolated human hepatocytes: Relevance to liver cell transplantation Liver Transpl. 2007 13 599 606 10.1002/lt.21128 17394166 · DOI
- [14]Beuneu C. Vosters O. Movahedi B. Remmelink M. Salmon I. Pipeleers D. Pradier O. Goldman M. Verhasselt V. Human pancreatic duct cells exert tissue factor-dependent procoagulant activity: Relevance to islet transplantation Diabetes 2004 53 1407 1411 10.2337/diabetes.53.6.1407 15161741 · DOI
- [15]Moll G. Rasmusson-Duprez I. von Bahr L. Connolly-Andersen A.-M. Elgue G. Funke L. Hamad O.A. Lönnies H. Magnusson P.U. Sanchez J. Are therapeutic human mesenchymal stromal cells compatible with human blood? Stem Cells 2012 30 1565 1574 10.1002/stem.1111 22522999 · DOI
- [16]Christy B.A. Herzig M.C. Montgomery R.K. Delavan C. Bynum J.A. Reddoch K.M. Cap A.P. Procoagulant activity of human mesenchymal stem cells J. Trauma Acute Care Surg. 2017 83 S164 S169 10.1097/TA.0000000000001485 28628602 · DOI
- [17]Liao L. Shi B. Chang H. Su X. Zhang L. Bi C. Shuai Y. Du X. Deng Z. Jin Y. Heparin improves BMSC cell therapy: Anticoagulant treatment by heparin improves the safety and therapeutic effect of bone marrow-derived mesenchymal stem cell cytotherapy Theranostics 2017 7 106 116 10.7150/thno.16911 28042320 PMC5196889 · DOI
- [18]Spronk H.M.H. ten Cate H. van der Meijden P.E.J. Differential roles of tissue factor and phosphatidylserine in activation of coagulation Thromb. Res. 2014 133 Suppl. 1 S54 S56 10.1016/j.thromres.2014.03.022 24759145 · DOI
- [19]Stephenne X. Nicastro E. Eeckhoudt S. Hermans C. Nyabi O. Lombard C. Najimi M. Sokal E. Bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity PLoS ONE 2012 7 e42819 10.1371/journal.pone.0042819 22900053 PMC3416788 · DOI
- [20]Makatsaria A.D. Bitsadze V.O. Akinshina S.V. Severe forms of preeclampsia as a manifestation of thrombotic microangiopathy Akusherstvo i Ginekologiya (Russian Federation) 2017 21 26 10.18565/aig.2017.4.21-6 · DOI
- [21]Shamshirsaz A.A. Paidas M. Krikun G. Preeclampsia, hypoxia, thrombosis, and inflammation J. Pregnancy 2012 2012 374047 10.1155/2012/374047 22175023 PMC3235807 · DOI
- [22]Saracco P. Bagna R. Gentilomo C. Magarotto M. Viano A. Magnetti F. Giordano P. Luciani M. Molinari A.C. Suppiej A. Neonatal Working Group of Registro Italiano Trombosi Infantili (RITI) Clinical Data of Neonatal Systemic Thrombosis J. Pediatr. 2016 171 60 66.e1 10.1016/j.jpeds.2015.12.035 26787378 · DOI
- [23]Sukhikh G.T. Silachev D.N. Goryunov K.V. Volochaeva M.V. Shmakov R.G. Role of stem cell dysfunction in the development of great obstetrical syndromes Akusherstvo i Ginekologiya (Russian Federation) 2018 5 11 10.18565/aig.2018.7.5-11 · DOI
- [24]Zhu Y. Xu L. Collins J.J.P. Vadivel A. Cyr-Depauw C. Zhong S. Mense L. Möbius M.A. Thébaud B. Human Umbilical Cord Mesenchymal Stromal Cells Improve Survival and Bacterial Clearance in Neonatal Sepsis in Rats Stem Cells Dev. 2017 26 1054 1064 10.1089/scd.2016.0329 28401804 · DOI
- [25]Levi M. van der Poll T. Inflammation and coagulation Crit. Care Med. 2010 38 S26 S34 10.1097/CCM.0b013e3181c98d21 20083910 · DOI
- [26]Franquesa M. Hoogduijn M.J. Ripoll E. Luk F. Salih M. Betjes M.G.H. Torras J. Baan C.C. Grinyó J.M. Merino A.M. Update on controls for isolation and quantification methodology of extracellular vesicles derived from adipose tissue mesenchymal stem cells Front. Immunol. 2014 5 525 10.3389/fimmu.2014.00525 25374572 PMC4204528 · DOI
- [27]Soshitova N.P. Karamzin S.S. Balandina A.N. Fadeeva O.A. Kretchetova A.V. Galstian G.M. Panteleev M.A. Ataullakhanov F.I. Predicting prothrombotic tendencies in sepsis using spatial clot growth dynamics Blood Coagul. Fibrinolysis 2012 23 498 507 10.1097/MBC.0b013e328352e90e 22688554 · DOI
- [29]Wiśniewski J.R. Zougman A. Nagaraj N. Mann M. Universal sample preparation method for proteome analysis Nat. Methods 2009 6 359 362 10.1038/nmeth.1322 19377485 · DOI · Paper page
- [30]Kononikhin A.S. Starodubtseva N.L. Chagovets V.V. Ryndin A.Y. Burov A.A. Popov I.A. Bugrova A.E. Dautov R.A. Tokareva A.O. Podurovskaya Y.L. Exhaled breath condensate analysis from intubated newborns by nano-HPLC coupled to high resolution MS J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2017 1047 97 105 10.1016/j.jchromb.2016.12.036 28040456 · DOI
- [31]Perez-Riverol Y. Csordas A. Bai J. Bernal-Llinares M. Hewapathirana S. Kundu D.J. Inuganti A. Griss J. Mayer G. Eisenacher M. The PRIDE database and related tools and resources in 2019: Improving support for quantification data Nucleic Acids Res. 2019 47 D442 D450 10.1093/nar/gky1106 30395289 PMC6323896 · DOI
- [32]Davies J.E. Walker J.T. Keating A. Concise Review: Wharton’s Jelly: The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells Stem Cells Transl. Med. 2017 6 1620 1630 10.1002/sctm.16-0492 28488282 PMC5689772 · DOI
- [33]Kim D.-W. Staples M. Shinozuka K. Pantcheva P. Kang S.-D. Borlongan C.V. Wharton’s jelly-derived mesenchymal stem cells: Phenotypic characterization and optimizing their therapeutic potential for clinical applications Int. J. Mol. Sci. 2013 14 11692 11712 10.3390/ijms140611692 23727936 PMC3709752 · DOI
- [34]Phinney D.G. Pittenger M.F. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy Stem Cells 2017 35 851 858 10.1002/stem.2575 28294454 · DOI · Paper page
- [35]Roy S. Hochberg F.H. Jones P.S. Extracellular vesicles: The growth as diagnostics and therapeutics; a survey J. Extracell. Vesicles 2018 7 1438720 10.1080/20013078.2018.1438720 29511461 PMC5827771 · DOI
- [36]György B. Hung M.E. Breakefield X.O. Leonard J.N. Therapeutic applications of extracellular vesicles: Clinical promise and open questions Annu. Rev. Pharmacol. Toxicol. 2015 55 439 464 10.1146/annurev-pharmtox-010814-124630 25292428 PMC4445965 · DOI
- [37]Maji S. Yan I.K. Parasramka M. Mohankumar S. Matsuda A. Patel T. In vitro toxicology studies of extracellular vesicles J. Appl. Toxicol. 2017 37 310 318 10.1002/jat.3362 27435060 · DOI
- [38]Kim H.-S. Choi D.-Y. Yun S.J. Choi S.-M. Kang J.W. Jung J.W. Hwang D. Kim K.P. Kim D.-W. Proteomic analysis of microvesicles derived from human mesenchymal stem cells J. Proteome Res. 2012 11 839 849 10.1021/pr200682z 22148876 · DOI
- [39]Garnier D. Magnus N. Lee T.H. Bentley V. Meehan B. Milsom C. Montermini L. Kislinger T. Rak J. Cancer cells induced to express mesenchymal phenotype release exosome-like extracellular vesicles carrying tissue factor J. Biol. Chem. 2012 287 43565 43572 10.1074/jbc.M112.401760 23118232 PMC3527943 · DOI
- [40]Gardiner C. Harrison P. Belting M. Böing A. Campello E. Carter B.S. Collier M.E. Coumans F. Ettelaie C. van Es N. Extracellular vesicles, tissue factor, cancer and thrombosis—Discussion themes of the ISEV 2014 Educational Day J. Extracell. Vesicles 2015 4 26901 10.3402/jev.v4.26901 25773446 PMC4359985 · DOI
- [41]Moll G. Ignatowicz L. Catar R. Luecht C. Sadeghi B. Hamad O. Jungebluth P. Dragun D. Schmidtchen A. Ringdén O. Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua Stem Cells Dev. 2015 24 2269 2279 10.1089/scd.2015.0120 26192403 · DOI
- [42]Falanga A. Marchetti M. Vignoli A. Coagulation and cancer: Biological and clinical aspects J. Thromb. Haemost. 2013 11 223 233 10.1111/jth.12075 23279708 · DOI
- [43]Geddings J.E. Mackman N. Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients Blood 2013 122 1873 1880 10.1182/blood-2013-04-460139 23798713 PMC3772497 · DOI
- [44]Hu T. Bach R.R. Horton R. Konigsberg W.H. Todd M.B. Procoagulant activity in cancer cells is dependent on tissue factor expression Oncol. Res. 1994 6 321 327 7865907
- [45]Dvorak H.F. Van DeWater L. Bitzer A.M. Dvorak A.M. Anderson D. Harvey V.S. Bach R. Davis G.L. DeWolf W. Carvalho A.C. Procoagulant activity associated with plasma membrane vesicles shed by cultured tumor cells Cancer Res. 1983 43 4434 4442 6347372
- [46]Rao L.V. Tissue factor as a tumor procoagulant Cancer Metastasis Rev. 1992 11 249 266 1423817
- [47]Sugimura M. Donato R. Kakkar V.V. Scully M.F. Annexin V as a probe of the contribution of anionic phospholipids to the procoagulant activity of tumour cell surfaces Blood Coagul. Fibrinolysis 1994 5 365 373 8075308
- [48]Zhao L. Bi Y. Kou J. Shi J. Piao D. Phosphatidylserine exposing-platelets and microparticles promote procoagulant activity in colon cancer patients J. Exp. Clin. Cancer Res. 2016 35 54 10.1186/s13046-016-0328-9 27015840 PMC4807543 · DOI
- [49]Lai R.C. Lim S.K. Membrane Lipids Define Small Extracellular Vesicle Subtypes Secreted by Mesenchymal Stromal Cell J. Lipid Res. 2018 10.1194/jlr.R087411 30154233 PMC6358289 · DOI
- [50]van der Poll T. Herwald H. The coagulation system and its function in early immune defense Thromb. Haemost. 2014 112 640 648 10.1160/TH14-01-0053 24696161 · DOI
- [51]Gleeson B.M. Martin K. Ali M.T. Kumar A.H.S. Pillai M.G.-K. Kumar S.P.G. O’Sullivan J.F. Whelan D. Stocca A. Khider W. Bone Marrow-Derived Mesenchymal Stem Cells Have Innate Procoagulant Activity and Cause Microvascular Obstruction Following Intracoronary Delivery: Amelioration by Antithrombin Therapy Stem Cells 2015 33 2726 2737 10.1002/stem.2050 25969127 · DOI
- [52]Tripisciano C. Weiss R. Eichhorn T. Spittler A. Heuser T. Fischer M.B. Weber V. Different Potential of Extracellular Vesicles to Support Thrombin Generation: Contributions of Phosphatidylserine, Tissue Factor, and Cellular Origin Sci. Rep. 2017 7 6522 10.1038/s41598-017-03262-2 28747771 PMC5529579 · DOI
- [53]Kapustin A.N. Schoppet M. Schurgers L.J. Reynolds J.L. McNair R. Heiss A. Jahnen-Dechent W. Hackeng T.M. Schlieper G. Harrison P. Prothrombin Loading of Vascular Smooth Muscle Cell-Derived Exosomes Regulates Coagulation and Calcification Arterioscler. Thromb. Vasc. Biol. 2017 37 e22 e32 10.1161/ATVBAHA.116.308886 28104608 · DOI
- [54]Semeraro F. Ammollo C.T. Morrissey J.H. Dale G.L. Friese P. Esmon N.L. Esmon C.T. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: Involvement of platelet TLR2 and TLR4 Blood 2011 118 1952 1961 10.1182/blood-2011-03-343061 21673343 PMC3158722 · DOI
- [55]Deguchi H. Sinha R.K. Marchese P. Ruggeri Z.M. Zilberman-Rudenko J. McCarty O.J.T. Cohen M.J. Griffin J.H. Prothrombotic skeletal muscle myosin directly enhances prothrombin activation by binding factors Xa and Va Blood 2016 128 1870 1878 10.1182/blood-2016-03-707679 27421960 PMC5054698 · DOI
- [56]Tsai J.-C. Lin Y.-W. Huang C.-Y. Lin C.-Y. Tsai Y.-T. Shih C.-M. Lee C.-Y. Chen Y.-H. Li C.-Y. Chang N.-C. The role of calpain-myosin 9-Rab7b pathway in mediating the expression of Toll-like receptor 4 in platelets: A novel mechanism involved in α-granules trafficking PLoS ONE 2014 9 e85833 10.1371/journal.pone.0085833 24489676 PMC3904858 · DOI
- [57]Griffith L. Slupsky J. Seehafer J. Boshkov L. Shaw A.R. Platelet activation by immobilized monoclonal antibody: Evidence for a CD9 proximal signal Blood 1991 78 1753 1759 1832992
- [58]Israels S.J. McMillan-Ward E.M. Palmitoylation supports the association of tetraspanin CD63 with CD9 and integrin alphaIIbbeta3 in activated platelets Thromb. Res. 2010 125 152 158 10.1016/j.thromres.2009.07.005 19640571 · DOI
- [59]Mangin P.H. Kleitz L. Boucheix C. Gachet C. Lanza F. CD9 negatively regulates integrin alphaIIbbeta3 activation and could thus prevent excessive platelet recruitment at sites of vascular injury J. Thromb. Haemost. 2009 7 900 902 10.1111/j.1538-7836.2009.03322.x 19228283 · DOI
- [60]Reutelingsperger C.P. van Heerde W.L. Annexin V, the regulator of phosphatidylserine-catalyzed inflammation and coagulation during apoptosis Cell. Mol. Life Sci. 1997 53 527 532 10.1007/s000180050067 9230931 PMC11147358 · DOI
- [61]Tsuda T. Yoshimura H. Hamasaki N. Effect of phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine on the activated factor X-prothrombin system Blood Coagul. Fibrinolysis 2006 17 465 469 10.1097/01.mbc.0000240919.72930.ee 16905950 · DOI
- [62]Zwaal R.F. Comfurius P. van Deenen L.L. Membrane asymmetry and blood coagulation Nature 1977 268 358 360 10.1038/268358a0 887167 · DOI
- [63]Eirin A. Zhu X.-Y. Puranik A.S. Woollard J.R. Tang H. Dasari S. Lerman A. van Wijnen A.J. Lerman L.O. Comparative proteomic analysis of extracellular vesicles isolated from porcine adipose tissue-derived mesenchymal stem/stromal cells Sci. Rep. 2016 6 36120 10.1038/srep36120 27786293 PMC5081562 · DOI
- [64]Chen J. Ma Y. Wang Z. Wang H. Wang L. Xiao F. Wang H. Tan J. Guo Z. Thrombin promotes fibronectin secretion by bone marrow mesenchymal stem cells via the protease-activated receptor mediated signalling pathways Stem Cell Res. Ther. 2014 5 36 10.1186/scrt424 24636778 PMC4055141 · DOI
- [65]Shiratsuki S. Terai S. Murata Y. Takami T. Yamamoto N. Fujisawa K. Burganova G. Quintanilha L.F. Sakaida I. Enhanced survival of mice infused with bone marrow-derived as compared with adipose-derived mesenchymal stem cells Hepatol. Res. 2015 45 1353 1359 10.1111/hepr.12507 25692387 · DOI
- [66]Galipeau J. Sensébé L. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities Cell Stem Cell 2018 22 824 833 10.1016/j.stem.2018.05.004 29859173 PMC6434696 · DOI · Paper page
- [67]Gatti S. Bruno S. Deregibus M.C. Sordi A. Cantaluppi V. Tetta C. Camussi G. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury Nephrol. Dial. Transplant. 2011 26 1474 1483 10.1093/ndt/gfr015 21324974 · DOI
- [68]Bruno S. Grange C. Collino F. Deregibus M.C. Cantaluppi V. Biancone L. Tetta C. Camussi G. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury PLoS ONE 2012 7 e33115 10.1371/journal.pone.0033115 22431999 PMC3303802 · DOI
- [69]Choi M.R. Kim H.Y. Park J.-Y. Lee T.Y. Baik C.S. Chai Y.G. Jung K.H. Park K.S. Roh W. Kim K.S. Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis Neurosci. Lett. 2010 472 94 98 10.1016/j.neulet.2010.01.054 20117176 · DOI
- [70]Barbosa da Fonseca L.M. Gutfilen B. Rosado de Castro P.H. Battistella V. Goldenberg R.C.S. Kasai-Brunswick T. Chagas C.L.R. Wajnberg E. Maiolino A. Salles Xavier S. Migration and homing of bone-marrow mononuclear cells in chronic ischemic stroke after intra-arterial injection Exp. Neurol. 2010 221 122 128 10.1016/j.expneurol.2009.10.010 19853605 · DOI
- [71]Silachev D.N. Kondakov A.K. Znamenskii I.A. Kurashvili Y.B. Abolenskaya A.V. Antipkin N.R. Danilina T.I. Manskikh V.N. Gulyaev M.V. Pirogov Y.A. The Use of Technetium-99m for Intravital Tracing of Transplanted Multipotent Stromal Cells Bull. Exp. Biol. Med. 2016 162 153 159 10.1007/s10517-016-3565-1 27882463 · DOI
- [72]Hirsh J. Anand S.S. Halperin J.L. Fuster V. American Heart Association Guide to anticoagulant therapy: Heparin: A statement for healthcare professionals from the American Heart Association Circulation 2001 103 2994 3018 10.1161/01.CIR.103.24.2994 11413093 · DOI
- [73]Ling L. Camilleri E.T. Helledie T. Samsonraj R.M. Titmarsh D.M. Chua R.J. Dreesen O. Dombrowski C. Rider D.A. Galindo M. Effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells Gene 2016 576 292 303 10.1016/j.gene.2015.10.039 26484394 PMC5330685 · DOI
Cited by
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Mesenchymal stem cell secretome for regenerative medicine: Where do we stand?
Trigo, C. M., Rodrigues, J. S., Camões, S. P., Solá, S., & Miranda, J. P. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2024.05.004 · Cited by 205 · see citing works
“Nevertheless, the risk of thrombosis cannot be ignored, especially for higher concentrations, due to the presence of procoagulant factors when systemically administered [241,257].”
Strategies for the use of Extracellular Vesicles for the Delivery of Therapeutics
Sil, S., Dagur, R. S., Liao, K., Peeples, E. S., Hu, G., Periyasamy, P., & Buch, S. (2020) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09873-y · Cited by 109 · see citing works
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- Authors
- Silachev, D., Goryunov, K., Shpilyuk, M., Beznoschenko, O., Morozova, N., Kraevaya, E., Popkov, V., Pevzner, I., Zorova, L., Evtushenko, E., Starodubtseva, N., Kononikhin, A., Bugrova, A., Evtushenko, E., Plotnikov, E., Zorov, D., & Sukhikh, G.
- Affiliations
- Lomonosov Moscow State University (RU)
- National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of the Ministry of Healthcare of the Russian Federation (RU)
- V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117198, Russia
- Moscow Institute of Physics and Technology (RU)
- Russian Academy of Sciences (RU)
- Sechenov University (RU)
- Corresponding author
- Plotnikov, Egor
- Zorov, Dmitry
- ORCID
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2019-03-19
- Volume
- 8
- Issue
- 3
- Pages
- 258
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC6468445
- OpenAlex
- W2921050683
- Cited by
- 154
- References
- 1
- Citations by year
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- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
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- Cells (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Council on grants of the President of the Russian Federation (MD-2065.2018.4)
- Russian Science Foundation (19-14-00173)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- mesenchymal stem cells, umbilical cord-derived stem cells, extracellular vesicles, coagulation, procoagulant activity, thrombosis, heparin, tissue factor, phosphatidylserine, annexin V, platelet-free plasma
- MeSH terms
- Extracellular Vesicles, Adult, Anticoagulants, Blood Coagulation, Blood Platelets, Heparin, Humans, Infant, Newborn, Phosphatidylserines, Mesenchymal Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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