Platelet decoys inhibit thrombosis and prevent metastatic tumor formation in preclinical models. Sci Transl Med 2019 Feb 13;11(479)
Date
02/15/2019Pubmed ID
30760580DOI
10.1126/scitranslmed.aau5898Scopus ID
2-s2.0-85061618001 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
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.
Author List
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 DEAuthors
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinTadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBlood Platelets
Cell Line, Tumor
Disease Models, Animal
Extracellular Matrix
Female
Humans
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis
Platelet Adhesiveness
Platelet Aggregation
Rabbits
Receptors, Cell Surface
Thrombosis
