Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS

BACKGROUND Whether airspace biomarkers add value to plasma biomarkers in studying ARDS is not well understood. Mesenchymal stromal cells (MSCs) are an investigational therapy for ARDS, and airspace biomarkers may provide mechanistic evidence for MSCs' impact in patients with ARDS. METHODS We carried out a nested cohort study within a phase 2a safety trial of treatment with allogeneic MSCs for moderate to severe ARDS. Non-bronchoscopic bronchoalveolar lavage and plasma samples were collected 48 hours after study drug infusion. Airspace and plasma biomarker concentrations were compared between the MSC (n = 17) and placebo (n = 10) treatment arms, and correlation between the two compartments was tested. Airspace biomarkers were also tested for associations with clinical and radiographic outcomes. RESULTS Compared to placebo, MSC treatment significantly reduced airspace total protein, angiopoietin-2 (Ang-2), interleukin-6 (IL-6), and soluble tumor necrosis factor receptor-1 concentrations. Plasma biomarkers did not differ between groups. Each 10-fold increase in airspace Ang-2 was independently associated with 6.7 fewer days alive and free of mechanical ventilation (95% CI -12.3 to -1.0, p = 0.023), and each 10-fold increase in airspace receptor for advanced glycation end-products (RAGE) was independently associated with a 6.6 point increase in day 3 radiographic assessment of lung edema score (95% CI 2.4 to 10.7, p = 0.004). CONCLUSIONS MSCs reduced biological evidence of lung injury in patients with ARDS. Biomarkers from the airspaces provide additional value for studying pathogenesis, treatment effects, and outcomes in ARDS. TRIAL REGISTRATION NCT02097641 FUNDING. National Heart, Lung, and Blood Institute .