Prospective Therapeutic Applications of Platelet Extracellular Vesicles

Platelet concentrates are a licensed medicinal cellular product for hospital-based transfusion and are used as raw materials to prepare platelet lysates for human cell propagation. Platelet concentrates can be used to generate platelet-derived extracellular vesicles (p-EVs) for novel therapeutic indications in regenerative medicine and as drug-delivery vehicles. Using platelets as a source of EVs can alleviate the industrial and regulatory challenges associated with EVs generated from in vitro-expanded mesenchymal stromal cells. Procedures are under development to define downstream industrial manufacturing processes, pathogen safety measures, quality controls, and release criteria for p-EVs. Research and industrial collaborations among blood establishments, the biotech and cell therapy industries, bioindustry suppliers, and regulators are vital to accelerate clinical translation. There is much interest in the use of extracellular vesicles (EVs) as a subcellular therapy for regenerative medicine and drug delivery. Blood-borne platelets represent a source of therapeutic EVs that is so far largely unexplored. Advantages of platelets as a cellular source of EVs include their established clinical value, regulated collection procedures, availability in a concentrated form, propensity to generate EVs, and unique composition and tissue-targeting capacity. This review analyzes the unique potential of platelet-derived (p-) EVs as therapeutic modalities and presents their inherent translational advantages for hemostasis, for regenerative medicine, and as drug-delivery vehicles. There is much interest in the use of extracellular vesicles (EVs) as a subcellular therapy for regenerative medicine and drug delivery. Blood-borne platelets represent a source of therapeutic EVs that is so far largely unexplored. Advantages of platelets as a cellular source of EVs include their established clinical value, regulated collection procedures, availability in a concentrated form, propensity to generate EVs, and unique composition and tissue-targeting capacity. This review analyzes the unique potential of platelet-derived (p-) EVs as therapeutic modalities and presents their inherent translational advantages for hemostasis, for regenerative medicine, and as drug-delivery vehicles. secretory organelles of platelets that contain growth factors, cytokines, chemokines, and coagulation factors released on platelet activation and degranulation. an authorized facility responsible for any aspect of the collection and testing of human blood or blood components and their processing, storage, and distribution when intended for transfusion or further manufacture (WHO definition). secretory organelles of platelets that contain polyphosphate, ADP, ATP, calcium ions, and neurotransmitters. all production steps implemented to purify and formulate p-EVs into a product meeting the intended quality specification for clinically related applications. a physical phenomenon that is thought to favor the accumulation of nanosized particles (possibly including p-EVs) preferentially in tumor tissues. medicines that satisfy the priority healthcare needs of a population, considering disease prevalence and public health relevance, evidence of clinical efficacy and safety, and comparative costs and cost-effectiveness (adapted from the WHO definition). a heterogeneous population of cell-derived particles, most of less than 500–1000 nm, delimited by a lipid bilayer and unable to replicate due to lack of a functional nucleus. a legally binding system, part of quality assurance, to ensure that EV products can consistently be produced and controlled according to quality standards approved by regulatory authorities. a physiological process controlled by coagulation factors and platelets to prevent or stop bleeding. transmembrane glycoproteins present on platelet membranes that are capable of binding to ligands in the blood circulation or on other cells. national medicine regulatory authority, which should promulgate and enforce medicine regulations. a dedicated and validated treatment specifically intended to destroy or remove the infectivity of pathogens (e.g., viruses, bacteria, parasites) that may be present in starting platelet concentrates. an anucleated blood cell of 2–3 μm with a lifespan of 7–10 days in the blood circulation that is best known as being instrumental in controlling hemorrhaging. Platelets also modulate immunological, inflammatory, and repair mechanisms. They contain numerous factors (growth factors, cytokines, coagulation factors, etc.) and noncoding RNA, which contribute to tissue repair and regeneration. a therapeutic blood product on the WHO Model List of Essential Medicines, produced from whole-blood donations or by apheresis procedures, used to treat acquired or congenital bleeding disorders associated with platelet depletion or dysfunction. a complex, proteinaceous fluid rich in various nutrients and growth factors, which is obtained by the lysis or activation (degranulation) of platelets. The terminology ‘platelet releasate’ may also be used when the degranulation is triggered by a platelet agonist, like thrombin, rather than by physical disruption of platelet membranes. automatic dedicated collection procedure of platelets assisted by an apheresis machine whereby blood is taken from a donor and separated by physical means to recover a concentrate of platelets that is suspended in 100% plasma or a mixture of plasma and platelet additive solution. branch of medicine that promotes tissue healing, repair, and regeneration through the use of a range of therapies and clinical procedures. a formulation where a vehicle actively delivers a therapy in an appropriate manner to the desired site using a synthetic or physiological carrier and under conditions intended to limit systemic toxicity. a procedure whereby a single donation of blood is collected into a plastic bag system containing an anticoagulant and a RBC-stabilizing solution.