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Human mesenchymal stromal cells inhibit platelet activation and aggregation involving CD73-converted adenosine

Netsch, P. ; Elvers-Hornung, S. ; Uhlig, S. ; Klüter, H. ; Huck, V. ; Kirschhöfer, F. ; Weiß, G. ; Janetzko, K. ; Solz, H. ; Wuchter, P. ; Bugert, P. ; Bieback, K.

In: Stem Cell Research & Therapy, 9 (2018), Nr. 184. pp. 1-17. ISSN 1757-6512

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Download (2MB) | Lizenz: Creative Commons LizenzvertragHuman mesenchymal stromal cells inhibit platelet activation and aggregation involving CD73-converted adenosine by Netsch, P. ; Elvers-Hornung, S. ; Uhlig, S. ; Klüter, H. ; Huck, V. ; Kirschhöfer, F. ; Weiß, G. ; Janetzko, K. ; Solz, H. ; Wuchter, P. ; Bugert, P. ; Bieback, K. underlies the terms of Creative Commons Attribution 3.0 Germany

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Abstract

Background: Mesenchymal stromal cells (MSCs) are promising cell therapy candidates. Clinical application is considered safe. However, minor side effects have included thromboembolism and instant blood-mediated inflammatory reactions suggesting an effect of MSC infusion on hemostasis. Previous studies focusing on plasmatic coagulation as a secondary hemostasis step detected both procoagulatory and anticoagulatory activities of MSCs. We now focus on primary hemostasis and analyzed whether MSCs can promote or inhibit platelet activation.

Methods: Effects of MSCs and MSC supernatant on platelet activation and function were studied using flow cytometry and further platelet function analyses. MSCs from bone marrow (BM), lipoaspirate (LA) and cord blood (CB) were compared to human umbilical vein endothelial cells or HeLa tumor cells as inhibitory or activating cells, respectively.

Results: BM-MSCs and LA-MSCs inhibited activation and aggregation of stimulated platelets independent of the agonist used. This inhibitory effect was confirmed in diagnostic point-of-care platelet function analyses in platelet-rich plasma and whole blood. Using inhibitors of the CD39–CD73–adenosine axis, we showed that adenosine produced by CD73 ectonucleotidase activity was largely responsible for the LA-MSC and BM-MSC platelet inhibitory action. With CB-MSCs, batch-dependent responses were obvious, with some batches exerting inhibition and others lacking this effect.

Conclusions: Studies focusing on plasmatic coagulation suggested both procoagulatory and anticoagulatory activities of MSCs. We now show that MSCs can, dependent on their tissue origin, inhibit platelet activation involving adenosine converted from adenosine monophosphate by CD73 ectonucleotidase activity. These data may have strong implications for safety and risk/benefit assessment regarding MSCs from different tissue sources and may help to explain the tissue protective mode of action of MSCs. The adenosinergic pathway emerges as a key mechanism by which MSCs exert hemostatic and immunomodulatory functions.

Item Type: Article
Journal or Publication Title: Stem Cell Research & Therapy
Volume: 9
Number: 184
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 10 Jul 2018 12:47
Date: 2018
ISSN: 1757-6512
Page Range: pp. 1-17
Faculties / Institutes: Medizinische Fakultät Mannheim > Institut für Klinische Chemie
Medizinische Fakultät Mannheim > Institut für Transfusionsmedizin und Immunologie
Subjects: 610 Medical sciences Medicine
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