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

Abstract

Mesenchymal stromal cell (MSC) injection has afforded heterogenous outcomes in knee osteoarthritis (KOA). Herein, a framework that dually correlates KOA patient responsiveness to baseline autologous bone marrow-derived MSC(M) donor batch attributes and baseline clinical and biomarker features is provided. Using clinical trial data, we demonstrated that MSC(M) 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 Injury and Osteoarthritis Outcome Scores. Responder MSC(M) donor batches had unique microRNA expression and ability to polarize CD14+ monocytes in vitro. KOA Responders had lower baseline physical activity and trended toward more severe baseline KOA. Baseline local but not systemic biomarkers showed trending correlations to patient responsiveness. 42% of KOA patients were Responders at 24 months, emphasizing durability of single MSC(M) injections. Together, our analytical methodology defines critical quality attributes of potent MSC(M) donor batches and identifies putative KOA patient theratypes to MSC treatments. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/665028v4_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@18bbb07org.highwire.dtl.DTLVardef@a406e8org.highwire.dtl.DTLVardef@c18c8corg.highwire.dtl.DTLVardef@f2731c_HPS_FORMAT_FIGEXP M_FIG C_FIG