Responders vs. non-responders to mesenchymal stromal cells in knee osteoarthritis patients: mechanistic correlates of donor cell attributes and putative patient features

Mesenchymal stromal cells (MSCs) have resulted in heterogenous clinical effectiveness in knee osteoarthritis (KOA). Herein, a framework that dually correlates KOA patient responsiveness to baseline bone m arrow-derived MSC(M) donor batch attributes and baseline clinical and biomarker features is provided. Using previous clinical trial data, we demonstrated that MSCs with increased immunomodulatory potency are more efficacious. Multivariable MSC(M) genes correlated strongly with responder status and to 12- and 24-month improvements in Knee Osteoarthritis and Outcome Scores. Responder MSC(M) donor batches had differential microRNA expression and ability to polarize CD14+ monocytes in vitro . KOA Responders had more severe OA and lower physical activity. Baseline biomarkers showed trending correlations to patient responsiveness. 62.5% of KOA patients remained Responders at 8-10 years, speaking to longer-term effects of single MSC(M) injections. Thus, our analytical methodology defines critical quality attributes of potent MSC donor batches and identifies putative KOA patient theratypes to MSC treatments.