Integration of clinical and multi-omics data identifies changes in the composition and activity of autologous-conditioned plasma that correlate with outcomes in patients with knee osteoarthritis

Autologous blood-derived products such as platelet-rich plasma (PRP) or autologous-conditioned plasma (ACP) have been used for managing symptoms of knee osteoarthritis (OA); however, the outcomes are highly variable due to limited information about the characteristics of these products, and how they impact clinical responses. We hypothesized that the clinical response ACP in patients with knee OA will correlate with the biologic activity and composition of the ACP administered. To test our hypothesis, we enrolled 51 patients with mild-moderate knee OA. We collected clinical information at baseline, and patient reported outcomes at 6 weeks and 6 months after ACP injection. We evaluated the composition of ACP by multiplex ELISA, and the biologic activity of the same aliquots using an in vitro biologic assay paired with gene expression analyses. Patients were stratified as responders and non-responders to ACP based on achievement of minimal clinically important differences in patient reported outcomes collected at 6 weeks and 6 months. RNA sequencing revealed that ACP modulates inflammatory responses in a co-culture of macrophages and fibroblast-like synoviocytes (fibroblasts); using this data, we selected specific genes to evaluate the biologic activity of ACP in vitro. Comparison of ACP from responders and non-responders revealed differences in the composition and activity of ACP between these groups. By integrating clinical and multi-omics data, we uncovered changes in the composition and biologic activity of ACP that may correlate with outcomes in knee OA patients. Overall design: Macrophages (n=4) and fibroblasts (n=4) were co-cultured in a 0.4 mm polyester trans-well system. The co-cultured cells were left untreated (control, medium) or incubated with 10% v:v of activated ACP, 20ng/ml of recombinant human TNF, or ACP+TNF for an additional 24 hours. At 24 h, RNA was isolated for RNA-seq.