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

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.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Papa AL,Jiang A,Korin N,Chen MB,Langan ET,Waterhouse A,Nash E,Caroff J,Graveline A,Vernet A,Mammoto A,Mammoto T,Jain A,Kamm RD,Gounis MJ,Ingber DE

doi

10.1126/scitranslmed.aau5898

subject

Has Abstract

pub_date

2019-02-13 00:00:00

issue

479

eissn

1946-6234

issn

1946-6242

pii

11/479/eaau5898

journal_volume

11

pub_type

杂志文章

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