Unraveling the Signaling Secretome of Platelet-Rich Plasma: Towards a Better Understanding of Its Therapeutic Potential in Knee Osteoarthritis

Abstract

Platelets and their secretory products play an important role in determining the balance between tissue repair and tissue damage. To obtain novel insights into the molecular composition of platelet-rich plasma (PRP) and contextualize them in knee osteoarthritis (OA), two different plasma formulations, namely PRP and platelet-poor plasma (PPP), were prepared from six healthy donors following a biobank-automated protocol. Inter-donor differences were analyzed, and pools were created before performing multiplexing protein arrays. In addition, PRP and PPP were prepared from six patients following our in-house protocols. Supernatants from PRP and PPP were harvested one hour after calcium chloride activation. Multiplexing protein arrays were performed in parallel for all plasma formulations. Results were normalized to fold change in relation to PPP and examined using Ingenuity Pathway Analysis Software. Bioinformatic predictions showed that PRPs constitute a signaling system with interrelated networks of inflammatory and angiogenic proteins, including but not limited to interleukin-6 and -8 (IL-6, IL-8), insulin like growth factor 1 (IGF-1), transforming growth factor beta, (TGF-b), and vascular endothelial growth factor (VEGF) signaling, underlying biological actions. Predictions of canonical systems activated with PRP molecules include various inflammatory pathways, including high-mobility group box protein (HMGB1) and interleukin 17 (IL-17) signaling, neuroinflammation, and nuclear factor-kappa b (NF-κB) pathways. Eventually, according to these predictions and OA evolving knowledge, selected PRP formulations should be tailored to modulate different inflammatory phenotypes, i.e., meta-inflammation, inflame-aging or posttraumatic inflammatory osteoarthritis. However, further research to discriminate the peculiarities of autologous versus allogeneic formulations and their effects on the various OA inflammatory phenotypes is needed to foster PRPs.

The Top 100 Most Cited Articles on Platelet-Rich Plasma Use in Regenerative Medicine—A Bibliometric Analysis—From the ESSKA Orthobiologic Initiative

“…PRP is an autologous biological product containing numerous bioactive proteins such as growth factors (IGF, TGF, VEGF, PDGF, etc. ), cytokines, and chemokines, which have the potential to play therapeutic roles in a variety of treatments, including musculoskeletal conditions, gynecology, urology, plastic surgery, ophthalmology, and dermatology, while its production remains easy, fast, and quite cheap to set up [ 9 , 10 , 11 ]. Indeed, PRP is simply obtained by the centrifugation of anticoagulated whole blood, allowing separation of plasma and platelets and having the lowest densities compared to red blood cells (RBCs) and leukocytes.…”

Wound-Microenvironment Engineering through Advanced-Dressing Bioprinting

“…In a recent study [ 53 ], we showed that the molecular intricacy of PRP by far exceeds that of PPP. In fact, platelet secretome contains a pool of chemokines, growth factors and interleukins, which are synthesized in the bone marrow by their parent cell, the megakaryocyte.…”

Biological Targets of Multimolecular Therapies in Middle-Age Osteoarthritis

“…63,64 Protein arrays followed by bioinformatic analyses have revealed an association between platelet secretome and osteoarthritis canonical pathway. 65 These analyses also predicted the participation of platelet secretome in specific inflammatory pathways, including neuroinflammation, IL-17, IL-6, IL-8, and high-mobility group box 1 signaling. 65 The molecular intricacies of PRP in immune cell modulation are depicted in Figure 1.…”

“…65 These analyses also predicted the participation of platelet secretome in specific inflammatory pathways, including neuroinflammation, IL-17, IL-6, IL-8, and high-mobility group box 1 signaling. 65 The molecular intricacies of PRP in immune cell modulation are depicted in Figure 1.…”