Autologous Platelet and Extracellular Vesicle-Rich Plasma as Therapeutic Fluid: A Review

Abstract

The preparation of autologous platelet and extracellular vesicle-rich plasma (PVRP) has been explored in many medical fields with the aim to benefit from its healing potential. In parallel, efforts are being invested to understand the function and dynamics of PVRP that is complex in its composition and interactions. Some clinical evidence reveals beneficial effects of PVRP, while some report that there were no effects. To optimize the preparation methods, functions and mechanisms of PVRP, its constituents should be better understood. With the intention to promote further studies of autologous therapeutic PVRP, we performed a review on some topics regarding PVRP composition, harvesting, assessment and preservation, and also on clinical experience following PVRP application in humans and animals. Besides the acknowledged actions of platelets, leukocytes and different molecules, we focus on extracellular vesicles that were found abundant in PVRP.

Keywords: centrifugation; extracellular vesicles; fresh-frozen plasma; intercellular signaling peptides and proteins; platelet-rich plasma; platelets; regeneration; small cellular particles; wound healing.

Figure 1

Micro and nano-sized plasma constituents. (A) Transmission Electron Micrograph (TEM) of an activated platelet showing budding of the tubular protrusion. (B) Scanning Electron Micrograph (SEM) of erythrocytes (parts shown in upper right corner), activated platelets and numerous EVs. (C) SEM of plasma after 15 h fasting. (D) SEM of plasma after a greasy meal revealing numerous lipid droplets (black arrows) and a few leukocytes (white triangle). (A): From Wolf, 1967, reprinted with permission from the British Journal of Haematology [46]. 2008, John Wiley and Sons (license number: 5458180157633). The sample shown in Panel (B) was prepared as described in [4]. The samples shown in Panel (C,D) were prepared as described in [47].

Figure 2

Selected images of EVs found in isolates from plasma. (A,B) Cryogenic Transmission Electron Micrographs (cryo-TEM) of EVs labeled with Anx5-, anti-CD235a- and anti-CD41-gold-NPs. White asterisks in (A,B) point to areas of the carbon net. Black arrows point to thin necks formed within the vesicles. Scale bars: 200 nm. (C,D,F,I,L): SEM of isolates from human plasma. (E,G,H,J,K): Cryo-TEM of isolates from plasma. (A,B), (E,J): Reproduced with permission from John Wiley and Sons, published by Journal of Extracellular Vesicles, 2013 (license number: 54583331312062) [60]. (D) From [10]. (I) Originally published by and used with permission from Dove Medical Press Ltd. [4]. Samples depicted in Panels (C,G,H,K) were prepared as described in [11]; samples (F,L) were prepared as described in [4].

Figure 3

A schematic display of PVRP and PVRP gel preparation. PVRP, platelet and vesicle-rich plasma. Source: Biorender.com.