Platelets, Protean Cells with All-Around Functions and Multifaceted Pharmacological Applications

Abstract

Platelets, traditionally known for their roles in hemostasis and coagulation, are the most prevalent blood component after erythrocytes (150,000-400,000 platelets/μL in healthy humans). However, only 10,000 platelets/μL are needed for vessel wall repair and wound healing. Increased knowledge of the platelet's role in hemostasis has led to many advances in understanding that they are crucial mediators in many other physiological processes, such as innate and adaptive immunity. Due to their multiple functions, platelet dysfunction is involved not only in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism, but also in several other disorders, such as tumors, autoimmune diseases, and neurodegenerative diseases. On the other hand, thanks to their multiple functions, nowadays platelets are therapeutic targets in different pathologies, in addition to atherothrombotic diseases; they can be used as an innovative drug delivery system, and their derivatives, such as platelet lysates and platelet extracellular vesicles (pEVs), can be useful in regenerative medicine and many other fields. The protean role of platelets, from the name of Proteus, a Greek mythological divinity who could take on different shapes or aspects, is precisely the focus of this review.

Keywords: extracellular vesicles; inflammation; platelet derivatives; platelets.

Figure 1

Platelet concentrate processing techniques. The upper part of the figure shows the preparation of P-PRP and L-PRP. The centrifugation steps allow the separation into PPP, buffy coat, and packed RBCs. The main difference between P-PRP and L-PRP derives from the amount of buffy coat collected between the first and the second centrifugation steps. In the lower part of the figure, PRF preparation is displayed: after blood collection in tubes without anticoagulant, a flexible and malleable fibrin clot is obtained through centrifugation. Created in BioRender.com (accessed on 17 Fabruary 2023). Abbreviations: L-PRP, leukocyte and platelet-rich plasma; PPP, platelet-poor plasma; P-PRP, pure platelet-rich plasma; RBC, red blood cell.

Figure 2

Main applications of platelet derivatives. Created in BioRender.com (accessed on 16 January 2023).

Figure 3

Cancer-platelet interplay. The cancer-platelet interaction is bidirectional. Cancer cells express several molecules able to interact with platelet receptors capable of forming aggregates of platelets and cancer cells, which leads to platelet activation and creation of a pro-thrombotic environment on one side, and to tumor cell extravasation on the other. In turn, platelet activation by cancer cells promotes the release of the platelet secretome, including proinflammatory cytokines and growth factors that promote tumor growth, modulate the tumor microenvironment by recruiting and activating leukocytes, and favor the formation of metastases. Furthermore, platelet-derived TGF-β decreases the NK cell patrolling activity, thus increasing tumor cell survival. Created in BioRender.com (accessed on 29 December 2022).

Figure 4

Platelet role in healthy brain function and association with neurodegenerative disorders. The left side of the figure shows, the role of platelets in brain physiological processes, including their modulation of neurogenesis and synaptogenesis through the release of bioactive molecules contained in their granules or platelet-derived exosomes and microparticles, their bridging function between the blood and the brain, and their contribution to neuronal communication through the release of neurotransmitters. In contrast, the right side displays their involvement in neurodegenerative processes such as their putative role in β-amyloid plaque formation in AD or metabolic dysregulation associated with Huntington’s disease. Created in BioRender.com (accessed on 12 January 2023).