Research ArticleTHROMBOSIS

Platelet decoys inhibit thrombosis and prevent metastatic tumor formation in preclinical models

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Science Translational Medicine  13 Feb 2019:
Vol. 11, Issue 479, eaau5898
DOI: 10.1126/scitranslmed.aau5898

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Deceiving platelets

Platelets play a key role in homeostasis; however, platelet activation also contributes to several disorders, including cardiac diseases and cancer. Platelet inhibitors have been developed; however, slow reversal time increases the risk of adverse events. Now, Papa et al. produced rapidly reversible drug-free antiplatelet agents by modifying human platelets. The modified platelets, called platelet decoys, prevented thrombus formation in rabbits. Moreover, platelet decoys decreased metastasis formation in a mouse model of breast cancer by preventing cancer cell extravasation. The results suggest that platelet decoys might be an effective rapidly reversible therapy for treating thrombosis and possibly metastasis formation.

Abstract

Platelets are crucial for normal hemostasis; however, their hyperactivation also contributes to many potentially lethal pathologies including myocardial infarction, stroke, and cancer. We hypothesized that modified platelets lacking their aggregation and activation capacity could act as reversible inhibitors of platelet activation cascades. Here, we describe the development of detergent-extracted human modified platelets (platelet decoys) that retained platelet binding functions but were incapable of functional activation and aggregation. Platelet decoys inhibited aggregation and adhesion of platelets on thrombogenic surfaces in vitro, which could be immediately reversed by the addition of normal platelets; in vivo in a rabbit model, pretreatment with platelet decoys inhibited arterial injury–induced thromboembolism. Decoys also interfered with platelet-mediated human breast cancer cell aggregation, and their presence decreased cancer cell arrest and extravasation in a microfluidic human microvasculature on a chip. In a mouse model of metastasis, simultaneous injection of the platelet decoys with tumor cells inhibited metastatic tumor growth. Thus, our results suggest that platelet decoys might represent an effective strategy for obtaining antithrombotic and antimetastatic effects.

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