Thrombogenic Risk Induced by Intravascular Mesenchymal Stem Cell Therapy: Current Status and Future Perspectives

Louise Coppin, Etienne Sokal, Xavier Stéphenne, Louise Coppin, Etienne Sokal, Xavier Stéphenne

Abstract

Mesenchymal stem cells (MSCs) are currently studied and used in numerous clinical trials. Nevertheless, some concerns have been raised regarding the safety of these infusions and the thrombogenic risk they induce. MSCs express procoagulant activity (PCA) linked to the expression of tissue factor (TF) that, when in contact with blood, initiates coagulation. Some even describe a dual activation of both the coagulation and the complement pathway, called Instant Blood-Mediated Inflammatory Reaction (IBMIR), explaining the disappointing results and low engraftment rates in clinical trials. However, nowadays, different approaches to modulate the PCA of MSCs and thus control the thrombogenic risk after cell infusion are being studied. This review summarizes both in vitro and in vivo studies on the PCA of MSC of various origins. It further emphasizes the crucial role of TF linked to the PCA of MSCs. Furthermore, optimization of MSC therapy protocols using different methods to control the PCA of MSCs are described.

Keywords: anticoagulants; cell- and tissue-based therapy; mesenchymal stem cells; thrombosis.

Conflict of interest statement

E.S. is a founder and scientific advisor for Promethera Biosciences and has founding shares and/or stock options. X.S. has a consultancy agreement with Promethera Biosciences. L.C. declares declare no conflict of interest.

Figures

Figure 1
Figure 1
Activation of the coagulation can be described in three phases: During the initiation phase, small amounts of thrombin (IIa) are generated, inducing an important amplification loop through activation of platelets and cofactors V and VIII during the amplification phase. A large amount of thrombin (IIa) is thus generated, leading to an efficient burst of all enzymatic reactions involved in the entire coagulation process. In turn, during the propagation phase, these vast amounts of thrombin (IIa) lead to large quantities of fibrin strains, the final product of coagulation, consolidating the blood clot.

References

    1. Moll G., Ankrum J.A., Kamhieh-Milz J., Bieback K., Ringden O., Volk H.D., Geissler S., Reinke P. Intravascular Mesenchymal Stromal/Stem Cell Therapy Product Diversification: Time for New Clinical Guidelines. Trends Mol. Med. 2019;25:149–163. doi: 10.1016/j.molmed.2018.12.006.
    1. Moll G., Rasmusson-Duprez I., von Bahr L., Connolly-Andersen A.M., Elgue G., Funke L., Hamad O.A., Lonnies H., Magnusson P.U., Sanchez J., et al. Are therapeutic human mesenchymal stromal cells compatible with human blood? Stem Cells (Dayt. Ohio) 2012;30:1565–1574. doi: 10.1002/stem.1111.
    1. 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. doi: 10.3349/ymj.2013.54.5.1293.
    1. Wu Z., Zhang S., Zhou L., Cai J., Tan J., Gao X., Zeng Z., Li D. Thromboembolism Induced by Umbilical Cord Mesenchymal Stem Cell Infusion: A Report of Two Cases and Literature Review. Transplant. Proc. 2017;49:1656–1658. doi: 10.1016/j.transproceed.2017.03.078.
    1. Sokal E.M., Stephenne X., Ottolenghi C., Jazouli N., Clapuyt P., Lacaille F., Najimi M., de Lonlay P., Smets F. Liver engraftment and repopulation by in vitro expanded adult derived human liver stem cells in a child with ornithine carbamoyltransferase deficiency. JIMD Rep. 2014;13:65–72. doi: 10.1007/8904_2013_257.
    1. Melmed G.Y., Pandak W.M., Casey K., Abraham B., Valentine J., Schwartz D., Awais D., Bassan I., Lichtiger S., Sands B., et al. Human Placenta-derived Cells (PDA-001) for the Treatment of Moderate-to-severe Crohn’s Disease: A Phase 1b/2a Study. Inflamm. Bowel Dis. 2015;21:1809–1816. doi: 10.1097/MIB.0000000000000441.
    1. Wang H., Strange C., Nietert P.J., Wang J., Turnbull T.L., Cloud C., Owczarski S., Shuford B., Duke T., Gilkeson G., et al. Autologous Mesenchymal Stem Cell and Islet Cotransplantation: Safety and Efficacy. Stem Cells Transl. Med. 2018;7:11–19. doi: 10.1002/sctm.17-0139.
    1. Perlee D., van Vught L.A., Scicluna B.P., Maag A., Lutter R., Kemper E.M., van ’t Veer C., Punchard M.A., Gonzalez J., Richard M.P., et al. 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 (Dayt. Ohio) 2018;36:1778–1788. doi: 10.1002/stem.2891.
    1. Dubois C., Panicot-Dubois L., Merrill-Skoloff G., Furie B., Furie B.C. Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo. Blood. 2006;107:3902–3906. doi: 10.1182/blood-2005-09-3687.
    1. Mangin P., Yap C.L., Nonne C., Sturgeon S.A., Goncalves I., Yuan Y., Schoenwaelder S.M., Wright C.E., Lanza F., Jackson S.P. Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRgamma deficiency. Blood. 2006;107:4346–4353. doi: 10.1182/blood-2005-10-4244.
    1. Furie B., Furie B.C. Mechanisms of thrombus formation. N. Engl. J. Med. 2008;359:938–949. doi: 10.1056/NEJMra0801082.
    1. Yun S.H., Sim E.H., Goh R.Y., Park J.I., Han J.Y. Platelet Activation: The Mechanisms and Potential Biomarkers. Biomed Res. Int. 2016;2016:9060143. doi: 10.1155/2016/9060143.
    1. Martin B.M., Samy K.P., Lowe M.C., Thompson P.W., Cano J., Farris A.B., Song M., Dove C.R., Leopardi F.V., Strobert E.A., et al. Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction. Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 2015;15:1241–1252. doi: 10.1111/ajt.13098.
    1. Fager A.M., Wood J.P., Bouchard B.A., Feng P., Tracy P.B. Properties of Procoagulant Platelets. Defin. Charact. Subpopul. Bind. A Funct. Prothrombinase. 2010;30:2400–2407. doi: 10.1161/ATVBAHA.110.216531.
    1. Lhermusier T., Chap H., Payrastre B. Platelet membrane phospholipid asymmetry: From the characterization of a scramblase activity to the identification of an essential protein mutated in Scott syndrome. J. Thromb. Haemost. JTH. 2011;9:1883–1891. doi: 10.1111/j.1538-7836.2011.04478.x.
    1. Walker C.P.R., Royston D. Thrombin generation and its inhibition: A review of the scientific basis and mechanism of action of anticoagulant therapies. BJA Br. J. Anaesth. 2002;88:848–863. doi: 10.1093/bja/88.6.848.
    1. Levi M. Diagnosis and treatment of disseminated intravascular coagulation. Int. J. Lab. Hematol. 2014;36:228–236. doi: 10.1111/ijlh.12221.
    1. Tatsumi K., Ohashi K., Matsubara Y., Kohori A., Ohno T., Kakidachi H., Horii A., Kanegae K., Utoh R., Iwata T., et al. Tissue factor triggers procoagulation in transplanted mesenchymal stem cells leading to thromboembolism. Biochem. Biophys. Res. Commun. 2013;431:203–209. doi: 10.1016/j.bbrc.2012.12.134.
    1. Hoffman M., Monroe D.M., 3rd A cell-based model of hemostasis. Thromb. Haemost. 2001;85:958–965.
    1. Palta S., Saroa R., Palta A. Overview of the coagulation system. Indian J. Anaesth. 2014;58:515–523. doi: 10.4103/0019-5049.144643.
    1. Bhaskar A. Classic theory of haemostasis Cell based model of haemostasis. Curr. Med. Issues J. Cmc Vellore. 2016;14:5.
    1. Butenas S. Tissue factor structure and function. Scientifica. 2012;2012:964862. doi: 10.6064/2012/964862.
    1. Lwaleed B.A., Cooper A.J., Voegeli D., Getliffe K. Tissue factor: A critical role in inflammation and cancer. Biol. Res. Nurs. 2007;9:97–107. doi: 10.1177/1099800407305733.
    1. Spronk H.M., ten Cate H., van der Meijden P.E. Differential roles of tissue factor and phosphatidylserine in activation of coagulation. Thromb. Res. 2014;133(Suppl. 1):S54–S56. doi: 10.1016/j.thromres.2014.03.022.
    1. Chu A.J. Tissue factor, blood coagulation, and beyond: An overview. Int. J. Inflamm. 2011;2011:367284. doi: 10.4061/2011/367284.
    1. Foley J.H., Conway E.M. Cross Talk Pathways Between Coagulation and Inflammation. Circ. Res. 2016;118:1392–1408. doi: 10.1161/CIRCRESAHA.116.306853.
    1. Sokal E.M. From hepatocytes to stem and progenitor cells for liver regenerative medicine: Advances and clinical perspectives. Cell Prolif. 2011;44(Suppl. 1):39–43. doi: 10.1111/j.1365-2184.2010.00730.x.
    1. Stephenne X., Najimi M., Ngoc D.K., Smets F., Hue L., Guigas B., Sokal E.M. Cryopreservation of human hepatocytes alters the mitochondrial respiratory chain complex 1. Cell Transplant. 2007;16:409–419. doi: 10.3727/000000007783464821.
    1. Kojayan G.G., Alexander M., Imagawa D.K., Lakey J.R.T. Systematic review of islet cryopreservation. Islets. 2018;10:40–49. doi: 10.1080/19382014.2017.1405202.
    1. Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F., Krause D., Deans R., Keating A., Prockop D., Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–317. doi: 10.1080/14653240600855905.
    1. Barry F.P., Murphy J.M. Mesenchymal stem cells: Clinical applications and biological characterization. Int. J. Biochem. Cell Biol. 2004;36:568–584. doi: 10.1016/j.biocel.2003.11.001.
    1. Li H., Shen S., Fu H., Wang Z., Li X., Sui X., Yuan M., Liu S., Wang G., Guo Q. Immunomodulatory Functions of Mesenchymal Stem Cells in Tissue Engineering. Stem Cells Int. 2019;2019:9671206. doi: 10.1155/2019/9671206.
    1. Ankrum J.A., Ong J.F., Karp J.M. Mesenchymal stem cells: Immune evasive, not immune privileged. Nat. Biotechnol. 2014;32:252–260. doi: 10.1038/nbt.2816.
    1. Zhao L., Chen S., Shi X., Cao H., Li L. A pooled analysis of mesenchymal stem cell-based therapy for liver disease. Stem Cell Res. Ther. 2018;9:72. doi: 10.1186/s13287-018-0816-2.
    1. Wang Y.H., Wu D.B., Chen B., Chen E.Q., Tang H. Progress in mesenchymal stem cell-based therapy for acute liver failure. Stem Cell Res. Ther. 2018;9:227. doi: 10.1186/s13287-018-0972-4.
    1. Frederik N., Thierry G., Pierre-François L., Luc L., Enev H.L., Victor V., Virginie B., Clerget-Chossat N., Sokal E. GS-16-Safety and tolerability of liver-derived stem cells (HepaStem) infused in patients with acute-on-chronic liver failure or acute decompensation: A European phase I/IIa open-labelled study. J. Hepatol. 2019;70:e83. doi: 10.1016/S0618-8278(19)30144-6.
    1. Kurtz A. Mesenchymal stem cell delivery routes and fate. Int. J. Stem Cells. 2008;1:1–7. doi: 10.15283/ijsc.2008.1.1.1.
    1. Smets F., Dobbelaere D., McKiernan P., Dionisi-Vici C., Broue P., Jacquemin E., Lopes A.I., Goncalves I., Mandel H., Pawlowska J., et al. Phase I/II Trial of Liver Derived Mesenchymal Stem Cells in Pediatric Liver Based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-Derived Progenitor Cells (HepaStem(R)) in Urea Cycle Disorders and Crigler-Najjar Syndrome patients. Transplantation. 2019;103:1903–1915. doi: 10.1097/tp.0000000000002605.
    1. De Becker A., Riet I.V. Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy? World J. Stem Cells. 2016;8:73–87. doi: 10.4252/wjsc.v8.i3.73.
    1. Brown C., McKee C., Bakshi S., Walker K., Hakman E., Halassy S., Svinarich D., Dodds R., Govind C.K., Chaudhry G.R. Mesenchymal stem cells: Cell therapy and regeneration potential. J. Tissue Eng. Regen. Med. 2019;13:1738–1755. doi: 10.1002/term.2914.
    1. Walsh T.J., Eggleston J.C., Cameron J.L. Portal hypertension, hepatic infarction, and liver failure complicating pancreatic islet autotransplantation. Surgery. 1982;91:485–487.
    1. Shapiro A.M., Lakey J.R., Rajotte R.V., Warnock G.L., Friedlich M.S., Jewell L.D., Kneteman N.M. Portal vein thrombosis after transplantation of partially purified pancreatic islets in a combined human liver/islet allograft. Transplantation. 1995;59:1060–1063. doi: 10.1097/00007890-199504150-00027.
    1. Koh A., Senior P., Salam A., Kin T., Imes S., Dinyari P., Malcolm A., Toso C., Nilsson B., Korsgren O., et al. Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success. Transplantation. 2010;89:465–471. doi: 10.1097/TP.0b013e3181c478fd.
    1. Kawahara T., Kin T., Kashkoush S., Gala-Lopez B., Bigam D.L., Kneteman N.M., Koh A., Senior P.A., Shapiro A.M. Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation. Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 2011;11:2700–2707. doi: 10.1111/j.1600-6143.2011.03717.x.
    1. Bennet W., Groth C.G., Larsson R., Nilsson B., Korsgren O. Isolated human islets trigger an instant blood mediated inflammatory reaction: Implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes. Upsala J. Med. Sci. 2000;105:125–133. doi: 10.1517/03009734000000059.
    1. Liuwantara D., Chew Y.V., Favaloro E.J., Hawkes J.M., Burns H.L., O’Connell P.J., Hawthorne W.J. Characterizing the Mechanistic Pathways of the Instant Blood-Mediated Inflammatory Reaction in Xenogeneic Neonatal Islet Cell Transplantation. Transplant. Direct. 2016;2:e77. doi: 10.1097/TXD.0000000000000590.
    1. Moberg L., Johansson H., Lukinius A., Berne C., Foss A., Kallen R., Ostraat O., Salmela K., Tibell A., Tufveson G., et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet (Lond. Engl.) 2002;360:2039–2045. doi: 10.1016/S0140-6736(02)12020-4.
    1. Naziruddin B., Iwahashi S., Kanak M.A., Takita M., Itoh T., Levy M.F. Evidence for instant blood-mediated inflammatory reaction in clinical autologous islet transplantation. Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 2014;14:428–437. doi: 10.1111/ajt.12558.
    1. Cabric S., Eich T., Sanchez J., Nilsson B., Korsgren O., Larsson R. A new method for incorporating functional heparin onto the surface of islets of Langerhans. Tissue Eng. Part C Methods. 2008;14:141–147. doi: 10.1089/ten.tec.2007.0312.
    1. Ozmen L., Ekdahl K.N., Elgue G., Larsson R., Korsgren O., Nilsson B. Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: Possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes. 2002;51:1779–1784. doi: 10.2337/diabetes.51.6.1779.
    1. Akima S., Hawthorne W.J., Favaloro E., Patel A., Blyth K., Mudaliar Y., Chapman J.R., O’Connell P.J. Tirofiban and activated protein C synergistically inhibit the Instant Blood Mediated Inflammatory Reaction (IBMIR) from allogeneic islet cells exposure to human blood. Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 2009;9:1533–1540. doi: 10.1111/j.1600-6143.2009.02673.x.
    1. Beuneu C., Vosters O., Ling Z., Pipeleers D., Pradier O., Goldman M., Verhasselt V. N-Acetylcysteine derivative inhibits procoagulant activity of human islet cells. Diabetologia. 2007;50:343–347. doi: 10.1007/s00125-006-0529-4.
    1. Wang J., Sun Z., Gou W., Adams D.B., Cui W., Morgan K.A., Strange C., Wang H. alpha-1 Antitrypsin Enhances Islet Engraftment by Suppression of Instant Blood-Mediated Inflammatory Reaction. Diabetes. 2017;66:970–980. doi: 10.2337/db16-1036.
    1. Nilsson B., Ekdahl K.N., Korsgren O. Control of instant blood-mediated inflammatory reaction to improve islets of Langerhans engraftment. Curr. Opin. Organ Transplant. 2011;16:620–626. doi: 10.1097/MOT.0b013e32834c2393.
    1. Berman D.M., Cabrera O., Kenyon N.M., Miller J., Tam S.H., Khandekar V.S., Picha K.M., Soderman A.R., Jordan R.E., Bugelski P.J., et al. Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model. Transplantation. 2007;84:308–315. doi: 10.1097/01.tp.0000275401.80187.1e.
    1. Johansson H., Lukinius A., Moberg L., Lundgren T., Berne C., Foss A., Felldin M., Kallen R., Salmela K., Tibell A., et al. Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation. Diabetes. 2005;54:1755–1762. doi: 10.2337/diabetes.54.6.1755.
    1. Gustafson E.K., Elgue G., Hughes R.D., Mitry R.R., Sanchez J., Haglund U., Meurling S., Dhawan A., Korsgren O., Nilsson B. The instant blood-mediated inflammatory reaction characterized in hepatocyte transplantation. Transplantation. 2011;91:632–638. doi: 10.1097/TP.0b013e31820ae459.
    1. Gustafson E., Hamad O.A., Deckmyn H., Barbu A., Ekdahl K.N., Nilsson B. Exposure of von Willebrand Factor on Isolated Hepatocytes Promotes Tethering of Platelets to the Cell Surface. Transplantation. 2019;103:1630–1638. doi: 10.1097/TP.0000000000002707.
    1. Gustafson E., Asif S., Kozarcanin H., Elgue G., Meurling S., Ekdahl K.N., Nilsson B. Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin. Cell Transplant. 2017;26:71–81. doi: 10.3727/096368916X692609.
    1. Hammel J.M., Elfeki S.K., Kobayashi N., Ito M., Cai J., Fearon D.T., Graham F.L., Fox I.J. Transplanted hepatocytes infected with a complement receptor type 1 (CR1)-containing recombinant adenovirus are resistant to hyperacute rejection. Transplant. Proc. 1999;31:939. doi: 10.1016/S0041-1345(99)00003-2.
    1. 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. doi: 10.1371/journal.pone.0042819.
    1. Moll G., Alm J.J., Davies L.C., von Bahr L., Heldring N., Stenbeck-Funke L., Hamad O.A., Hinsch R., Ignatowicz L., Locke M., et al. Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties? Stem Cells (Dayt. Ohio) 2014;32:2430–2442. doi: 10.1002/stem.1729.
    1. Moll G., Ignatowicz L., Catar R., Luecht C., Sadeghi B., Hamad O., Jungebluth P., Dragun D., Schmidtchen A., Ringden O. Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua. Stem Cells Dev. 2015;24:2269–2279. doi: 10.1089/scd.2015.0120.
    1. 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. doi: 10.1097/TA.0000000000001485.
    1. Gleeson B.M., Martin K., Ali M.T., Kumar A.H., Pillai M.G., Kumar S.P., O’Sullivan J.F., Whelan D., Stocca A., Khider W., et al. Bone Marrow-Derived Mesenchymal Stem Cells Have Innate Procoagulant Activity and Cause Microvascular Obstruction Following Intracoronary Delivery: Amelioration by Antithrombin Therapy. Stem Cells (Dayt. Ohio) 2015;33:2726–2737. doi: 10.1002/stem.2050.
    1. George M.J., Prabhakara K., Toledano-Furman N.E., Wang Y.W., Gill B.S., Wade C.E., Olson S.D., Cox C.S., Jr. Clinical Cellular Therapeutics Accelerate Clot Formation. Stem Cells Transl. Med. 2018;7:731–739. doi: 10.1002/sctm.18-0015.
    1. Netsch P., Elvers-Hornung S., Uhlig S., Kluter H., Huck V., Kirschhofer F., Brenner-Weiss G., Janetzko K., Solz H., Wuchter P., et al. Human mesenchymal stromal cells inhibit platelet activation and aggregation involving CD73-converted adenosine. Stem Cell Res. Ther. 2018;9:184. doi: 10.1186/s13287-018-0936-8.
    1. 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. doi: 10.7150/thno.16911.
    1. Coppin L., Najimi M., Bodart J., Rouchon M.S., van der Smissen P., Eeckhoudt S., Dahlqvist G., Castanares-Zapatero D., Komuta M., Brouns S.L., et al. Clinical Protocol to Prevent Thrombogenic Effect of Liver-Derived Mesenchymal Cells for Cell-Based Therapies. Cells. 2019;8:846. doi: 10.3390/cells8080846.
    1. Vulliet P.R., Greeley M., Halloran S.M., MacDonald K.A., Kittleson M.D. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet (Lond. Engl.) 2004;363:783–784. doi: 10.1016/S0140-6736(04)15695-X.
    1. Oeller M., Laner-Plamberger S., Hochmann S., Ketterl N., Feichtner M., Brachtl G., Hochreiter A., Scharler C., Bieler L., Romanelli P., et al. Selection of Tissue Factor-Deficient Cell Transplants as a Novel Strategy for Improving Hemocompatibility of Human Bone Marrow Stromal Cells. Theranostics. 2018;8:1421–1434. doi: 10.7150/thno.21906.
    1. Moll G., Jitschin R., von Bahr L., Rasmusson-Duprez I., Sundberg B., Lonnies L., Elgue G., Nilsson-Ekdahl K., Mougiakakos D., Lambris J.D., et al. Mesenchymal stromal cells engage complement and complement receptor bearing innate effector cells to modulate immune responses. PLoS ONE. 2011;6:e21703. doi: 10.1371/journal.pone.0021703.
    1. Ettelaie C., Fountain D., Collier M.E., Elkeeb A.M., Xiao Y.P., Maraveyas A. Low molecular weight heparin downregulates tissue factor expression and activity by modulating growth factor receptor-mediated induction of nuclear factor-kappaB. Biochim. Et Biophys. Acta. 2011;1812:1591–1600. doi: 10.1016/j.bbadis.2011.09.007.
    1. Coppin L., Smets F., Ambroise J., Sokal E., Stéphenne X. Control of the thrombogenic risk with a combination of anticoagulant drugs during Liver Derived Mesenchymal Stem Cells infusions in 11 patients with Crigler-Najjar syndrome or Urea Cycle Disorders. J. Stem Cells Res. Dev. Ther. Under revision.
    1. Baygan A., Aronsson-Kurttila W., Moretti G., Tibert B., Dahllof G., Klingspor L., Gustafsson B., Khoein B., Moll G., Hausmann C., et al. Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for Graft-versus-Host Disease and Hemorrhagic Cystitis. Front. Immunol. 2017;8:795. doi: 10.3389/fimmu.2017.00795.
    1. Seeger F.H., Rasper T., Fischer A., Muhly-Reinholz M., Hergenreider E., Leistner D.M., Sommer K., Manavski Y., Henschler R., Chavakis E., et al. Heparin disrupts the CXCR4/SDF-1 axis and impairs the functional capacity of bone marrow-derived mononuclear cells used for cardiovascular repair. Circ. Res. 2012;111:854–862. doi: 10.1161/CIRCRESAHA.112.265678.
    1. Groeneveld D., Pereyra D., Veldhuis Z., Adelmeijer J., Ottens P., Kopec A.K., Starlinger P., Lisman T., Luyendyk J.P. Intrahepatic fibrin(ogen) deposition drives liver regeneration after partial hepatectomy in mice and humans. Blood. 2019;133:1245–1256. doi: 10.1182/blood-2018-08-869057.

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