Platelets are cells found circulating in the bloodstream, helping to form blood clots to stop bleeding and promote healing when a person is injured.  However, their hyperactivation can also contribute to lethal pathologies such as myocardial infarction, stroke, and cancer.  To counteract these several antiplatelet drugs have been developed to combat platelet-related conditions, however, their effects are not easily reversible, and patients taking these drugs are at risk of uncontrolled bleeding if injured. 

Now, a study from researchers led by Harvard University develops a rapidly reversible drug-free antiplatelet agent by modifying human platelets. The team states their synthetic modified platelets, called platelet decoys, prevented thrombus formation in rabbits, and decreased metastasis formation in a mouse model of breast cancer.  The opensource study is published in the journal Science Translational Medicine.

Artificial cells activate platelets

Previous studies indicate as the reversal of antiplatelet drugs requires the formation of new platelets, which takes at least 7 to 10 days, the use of antiplatelet drugs is a major risk factor for patients experiencing trauma or hemorrhage, where the need for the immediate reversal of antiplatelet therapy is critical.

Rapidly reversible platelet inhibitors would, therefore, be very useful for patients at high risk of bleeding complications or requiring emergency procedures.  The current study develops detergent-extracted human-modified platelet decoys capable of retaining platelet binding functions without the ability to functionally activate or aggregate.

The current study removes the lipid membrane and innards from human platelets in the lab via centrifugation and treatment with a detergent to produce the decoys.

Results show the platelet decoys inhibited aggregation and adhesion of platelets on thrombogenic surfaces in vitro, which could be immediately reversed by the addition of normal platelets.  Data findings show platelet decoys enable inhibition of platelet activation-dependent thrombosis in rodent and rabbit models, a mechanism rapidly reversed by adding additional functional platelets.

Artificial cells slow cancer growth

Results show decoys also inhibited platelet-mediated human breast cancer cell aggregation, and their presence decreased cancer cell arrest and extravasation in a microfluidic human microvasculature on a chip. Data findings show platelet decoys reduce metastasis formation in a mouse model, suggesting platelet decoys may also be useful for inhibiting platelet-mediated pathogenic processes associated with tumor progression.

The team surmises they have developed synthetic human platelet decoys as a reversible, drug-free, cell-based, antiplatelet therapy.   For the future, the researchers state their results suggest platelet decoys might be an effective rapidly reversible therapy for treating thrombosis and possibly metastasis formation.

Source: Wyss Institute at Harvard University

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