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.

Highlights

  • Autologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA)

  • After Institutional Review Board (IRB) approval (HSS IRB#2016-0267) and patient consent, 51 knee OA patients were enrolled in our study upon presentation to clinic and eligibility for platelet-rich-plasma (PRP) injection, following the inclusion and exclusion criteria indicated in Supplementary Table S1, including Kellgren-Lawrence OA grade 1–3 based on plain radiographs

  • We aimed to develop an integrative approach that permits the evaluation of PRP bioactivity in vitro, using PRP from patients with different responses to PRP

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Summary

Introduction

Autologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). The current view is that positive clinical results in OA patients are mainly related to the anti-inflammatory effects of PRP rather than to increased anabolic and reparative effects in articular c­ artilage[4,14] These reports are inconclusive because of the high variability in the available PRP preparations, the limited available information about the relevant characteristics in these blood products that impact clinical responses in patients with knee OA, the lack of consensus and standardization of treatment protocols and collection of outcomes, and the poor understanding of disease candidates or specific cell/tissue targets for a given ­therapy[15]

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