In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis

Abstract

Autologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

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

“…Indeed, bioinformatic predictions derived from this study confirm that PRP molecules influence inflammatory mechanisms and immune cell interactions. These results contravene current thinking and descriptions of PRPs focused above all on the growth factors [23,24] and their anabolic effects in chondrocytes as the basis of PRPs' mechanism of action. Although the proliferative and anabolic actions of PRPs have been shown in vitro [25], it seems improbable that chondrocytes embedded within the deteriorated cartilage could proliferate and synthesize ECM.…”

Intra-Articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Degree of Efficacy

“…Based on the patientreported results and accomplishment of minimal clinically important differences in patients with OA undergoing PRP injections, they identified responders and nonresponders to the treatment. Comparisons of PRP from these patient groups allowed them to identify differences in the composition and in vitro activity of PRP [76].…”

Effect of Combined Intraosseous and Intraarticular Infiltrations of Autologous Platelet-Rich Plasma on Subchondral Bone Marrow Mesenchymal Stromal Cells from Patients with Hip Osteoarthritis

“…Joint-sparing interventions such PRP IA injections are becoming popular in OA management [33]. The biological mechanisms behind PRP action and their links to improvements in clinical outcomes remain poorly understood but are believed to relate to both the PRP cellular composition and host (patient-related) factors [34][35][36]. In comparison to PRP joint injections, in which PRP primarily acts on the cartilage and synovium, IO PRP infiltrations provide an advantage of better access to the subchondral bone and bone-cartilage interface, potentially targeting the whole spectrum of OA-affected tissues.…”

“…While these molecules represent good candidates to take onto a larger study, other relevant pathways should also be considered. For example, a recent study investigating the in vitro responses of macrophages and synovial fibroblasts to PRP in patients with knee OA demonstrated that the pathways most significantly affected by PRP in fibroblasts, the cells the closest in nature to MSCs, were related to the cell cycle, DNA synthesis, and cell survival [34]. Future investigations should therefore investigate larger panels of genes, encompassing many more markers of cell proliferation, survival, and apoptosis as well as assess many inflammation-driven signalling pathways that might be activated in MSCs from OA joints.…”