In Vitro Assay to Predict the Clinical Response to Platelet Rich Plasma Treatment of Knee OA

About This Grant

Significance to VA: Osteoarthritis (OA) resulting from injury and progressive joint degeneration is a leading cause of disability for which there are no disease modifying drugs. Military service members suffer from OA at higher rates and younger ages than the general population. This massive disease burden from OA is therefore transferred and carried by the VA Healthcare System (VAHCS). Autologous platelet rich plasma (PRP) has been increasingly used clinically for symptomatic treatment of knee OA with variable clinical results. In a program to provide PRP injections to Veterans with symptomatic early knee OA at the VA Palo Alto (VAPA), clinically meaningful improvement in knee pain was achieved in less than 40% of PRP recipients at 6-months follow-up. However, those who improved continued to report better outcomes at 2-years follow-up. Thus, there is critical need for methods to predict clinical responsiveness. Our prior work has shown that PRP from different individuals has differing effects on macrophage inflammatory activity in vitro. We found that PRP from older Veterans with knee OA incited pro-inflammatory differentiation of healthy macrophages while that of young and healthy males did not. These findings underscore that PRP treatment may not be beneficial for all patients and demonstrate a clear need for biological screening. The goal of this pilot project is to explore whether an in vitro macrophage assay has potential to identify patients more likely to benefit from PRP injections for knee OA. Innovation and Impact: There are currently no in vitro assays or tests to predict individual responses to any OA treatment. The ability to predict individual patient responses to PRP injections will directly benefit Veterans and improve clinical care within the VAHCS by directing PRP treatment to those most likely to respond and sparing those unlikely to benefit the risks of undergoing an unnecessary procedure along with delay in referral for alternative care. The Specific Aims are: (Aim 1) To test the hypothesis that a patient’s clinical response to PRP treatment for knee OA can be predicted by the in vitro response of allogenic macrophages to treatment with (1a) patient-specific PRP or (1b) patient-specific platelet poor plasma (PPP); and (Aim 2) To test the hypothesis that a patient’s clinical response to PRP treatment for knee OA can be predicted by the in vitro response of autologous macrophages treated with (2a) patient-specific PRP or (2b) patient-specific PPP. The evaluation of patient- specific PPP (PS-PPP) will evaluate if this readily prepared blood fraction could serve as a surrogate for patient- specific PRP (PS-PRP) thereby facilitating the clinical use of a macrophage assay. Methodology: This pilot study will recruit Veterans receiving PRP injections for clinical treatment of symptomatic knee OA at the VAPA to contribute blood, PRP, and clinical outcomes. Changes in macrophage phenotypical differentiation following treatment with PS-PRP, specifically the ratio of pro-inflammatory M1 to anti-inflammatory M2 macrophages, will be measured using flow cytometry and immunoassays. These in vitro changes will be compared to patient- specific clinical outcomes, including changes in patient-perceived pain and gait function, assessed between baseline and 1-month follow-up as primary and secondary endpoints. Path to Translation/Implementation: This pilot study directly compares in vitro responses with a Veteran patient’s actual clinical response to PRP treatment. Should the proposed macrophage assays show potential to predict the clinical response to PRP, we will advance this work to a full clinical validation trial. This research aligns with the Rehabilitation Research, Development, and Translation (RDT) Broad Portfolio’s goal to improve Veteran mobility through precision medicine. Successful completion of this pilot project followed by broader validation in a full clinical trial could contribute a predictive assay into clinical use to improve the care of Veterans with OA and to support more efficient use of VA clinical resources.