Title

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

UMMS Affiliation

New England Center for Stroke Research, Department of Radiology

Publication Date

2019-02-13

Document Type

Article

Disciplines

Cardiovascular Diseases | Hemic and Immune Systems | Neoplasms | Nervous System Diseases | Radiology

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.

DOI of Published Version

10.1126/scitranslmed.aau5898

Source

Sci Transl Med. 2019 Feb 13;11(479). pii: eaau5898. doi: 10.1126/scitranslmed.aau5898. Link to article on publisher's site

Journal/Book/Conference Title

Science translational medicine

Related Resources

Link to Article in PubMed

PubMed ID

30760580

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