Synthetic platelet ‘decoys’ outsmart both clots and cancer.
Platelets are cells which circulate in the bloodstream and help 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 this 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 state 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.
Previous studies indicate as the reversal of antiplatelet drugs requires 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 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 which retain platelet binding functions and are incapable of functional activation or aggregation.
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 in a manner which can be rapidly reversed, simply by adding or infusing additional functional platelets.
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 that platelet decoys reduce metastasis formation in a mouse model, suggesting that platelet decoys may also be useful for inhibiting platelet-mediated pathogenic processes associated with tumour progression.
The team surmise 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 that platelet decoys might be an effective rapidly reversible therapy for treating thrombosis and possibly metastasis formation.