Scientists have developed a novel reversible, drug-free antiplatelet therapy that could reduce the risk of blood clots and potentially prevent cancer metastasis. The findings are published in Science Translational Medicine.
The therapeutic approach involves modifying human platelets to create "decoys" that are still capable of binding to some cells but will not aggregate or carry out the other normal platelet functions, including chemical signaling associated with the clotting process.
Bleeding Disorders
Bleeding disorder is an acquired or an inherited condition, which is characterized by excessive bleeding in the persons affected by the problem.
Advertisement
‘Preclinical study of deactivated platelets describes promising new approach to treating diseases. ’
Tweet it Now
"The reversibility and immediate onset of action are major advantages of our platelet decoys, and we envision them to be useful in hospital-based situations," Anne-Laure Papa, an assistant professor of biomedical engineering at the George Washington University, said. Dr. Papa was a postdoctoral fellow at Harvard University's Wyss Institute when the research was conducted. "The therapy could prevent clotting in high-risk patients just before they undergo surgery, or be given to cancer patients alongside chemotherapy to prevent existing tumors from spreading."
Platelets play a vital role in halting bleeding and help protect against minor and life-threatening bleeding. However, hyperactive platelets can also contribute to various disorders, including severe blood clots, heart disease and cancer. While several antiplatelet drugs fight clots, their effects are not easily reversible, leaving patients vulnerable if they develop unexpected severe bleeding or are in need of an emergency surgical procedure.
![New Immunotherapy Targets Blood-clotting Protein]( "New Immunotherapy Targets Blood-clotting Protein")
Scientists have used immunotherapy and stopped the detrimental effects of blood-brain barrier leaks to protect against multiple sclerosis and Alzheimer's disease.
Platelets also play an important part in cancer metastasis by binding to tumor cells and protecting them both from the body's immune system and shear stress as they circulate in the bloodstream. Platelets may also help the cancer cells exit through blood vessels and seed distant tissues during the process of metastasis.
To create the decoy platelets, the research team used a detergent treatment and centrifugation to strip natural human platelets of their inner structures and remove their basic activation and aggregation abilities. These decoy platelets became about one-third the size of a regular platelet while retaining a majority of adhesion receptors on their surface. This allows them to bind to other cells in the bloodstream, such as cancer cells, but not become active during the blood clotting process.
The researchers, led by Dr. Papa and Donald E. Ingber, the director of the Wyss Institute at Harvard University, first examined how the decoys might impede the formation of blood clots. The team injected the decoys into a microfluidic blood-vessel-mimicking device and observed how the decoys reacted to various platelet-stimulating chemicals. The researchers found the decoys did not show typical clotting behaviors, and when added to human blood within the device, the normal platelets showed a reduced ability to aggregate and create a clot by binding to the vessel's walls.
In addition, the researchers quickly reversed the effects of the decoys on normal platelets by introducing fresh platelets into the blood.
"Our ability to reverse the platelet inhibiting effects with a simple reintroduction of normal platelets is very encouraging as currently available anti-platelet agents are often difficult to reverse in emergency settings such as severe bleeding," Dr. Papa said.
Based on the key role platelets play in supporting cancer metastasis in the bloodstream, the team sought to target circulating tumor cells with their cellular approach. The decoy platelets were able to compete with normal platelets when binding to cancer cells and were effective in preventing cancer cell extrusion out of a vasculature-emulating microfluidic chip model. Furthermore, in a model of metastasis, there was a significant reduction in the burden of established metastatic tumors when cancer cells were introduced simultaneously with platelets and decoys.
In the future, the researchers will continue to work on this technology to enhance circulation time in comparison to platelets. They also hope to study whether platelet decoys can be used as drug transporters to target platelet-related conditions in the body.
Source: Eurekalert
New Immunotherapy Targets Blood-clotting Protein
Scientists have used immunotherapy and stopped the detrimental effects of blood-brain barrier leaks to protect against multiple sclerosis and Alzheimer's disease.
Advertisement
Platelets also play an important part in cancer metastasis by binding to tumor cells and protecting them both from the body's immune system and shear stress as they circulate in the bloodstream. Platelets may also help the cancer cells exit through blood vessels and seed distant tissues during the process of metastasis.
To create the decoy platelets, the research team used a detergent treatment and centrifugation to strip natural human platelets of their inner structures and remove their basic activation and aggregation abilities. These decoy platelets became about one-third the size of a regular platelet while retaining a majority of adhesion receptors on their surface. This allows them to bind to other cells in the bloodstream, such as cancer cells, but not become active during the blood clotting process.
The researchers, led by Dr. Papa and Donald E. Ingber, the director of the Wyss Institute at Harvard University, first examined how the decoys might impede the formation of blood clots. The team injected the decoys into a microfluidic blood-vessel-mimicking device and observed how the decoys reacted to various platelet-stimulating chemicals. The researchers found the decoys did not show typical clotting behaviors, and when added to human blood within the device, the normal platelets showed a reduced ability to aggregate and create a clot by binding to the vessel's walls.
In addition, the researchers quickly reversed the effects of the decoys on normal platelets by introducing fresh platelets into the blood.
"Our ability to reverse the platelet inhibiting effects with a simple reintroduction of normal platelets is very encouraging as currently available anti-platelet agents are often difficult to reverse in emergency settings such as severe bleeding," Dr. Papa said.
Based on the key role platelets play in supporting cancer metastasis in the bloodstream, the team sought to target circulating tumor cells with their cellular approach. The decoy platelets were able to compete with normal platelets when binding to cancer cells and were effective in preventing cancer cell extrusion out of a vasculature-emulating microfluidic chip model. Furthermore, in a model of metastasis, there was a significant reduction in the burden of established metastatic tumors when cancer cells were introduced simultaneously with platelets and decoys.
In the future, the researchers will continue to work on this technology to enhance circulation time in comparison to platelets. They also hope to study whether platelet decoys can be used as drug transporters to target platelet-related conditions in the body.
Source: Eurekalert
New Anti-clotting Drug Lowers Risk of Serious Bleeding
New drug known as direct oral anticoagulants (DOACs) is more effective than the older drug warfarin in decreasing the risk of severe bleeding.
Advertisement
 Trojan Horse Delivery for Treating Rare Blood Clotting Disorder DiscoveredTransfusion of rADAMTS13-loaded platelets may be a novel and potentially effective therapeutic approach for arterial thrombosis, associated with congenital and immune-mediated thrombotic thrombocytopenic purpura. | Advertisement
|
Advertisement
Recommended Reading
Latest Research News
Decoding the eight factors affecting Black adults' life expectancy.
Sobering truth about foot travel in the United States emerges from international statistics, highlighting the prevalence of walking on the Blacksburg campus.
Unveiling a hidden mechanism, proteins within brain cells exhibit newfound abilities at synapses, reinforcing Darwin's theory of adaptation and diversity in the natural world.
Combining micro-needling and cupping, two emerging and alternative techniques, in an experimental study reveals a potential synergy for skin rejuvenation.
Despite a decline in COVID-19 cases, the World Health Organisation (WHO) raises global concerns by warning of an "inevitable" next pandemic known as "Disease X".