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

Abstract

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 10.8, 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.

Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial

“…Future studies might determine if plasma biomarkers track the efficacy of multipotent adult progenitor cell therapy for ARDS, and whether they might be used to optimize dosing. However, there may be changes within the lung, evidenced by bronchoalveolar lavage but not detectable in circulation [ 33 ].…”

Mesenchymal Stromal/Stem Cells and Their Products as a Therapeutic Tool to Advance Lung Transplantation

“…Although the mechanisms are not fully defined yet, it has been widely demonstrated in both preclinical and clinical studies that therapeutic effects of MSCs are mediated, at least in part, by paracrine factors [ 21 , 22 , 23 , 24 ]. MSCs’ therapeutic properties have been also evaluated in a phase II clinical trial to treat acute respiratory distress syndrome (ARDS) [ 25 ]. MSCs and/or their products are able to mitigate both lung injury and inflammation in different experimental models, and the infusion of MSCs protects transplanted lungs from IRI [ 26 , 27 , 28 , 29 ].…”

Mesenchymal stem cell treatment for COVID-19

“… 71 , 72 , 73 , 74 , 75 , 76 In addition, MSCs simultaneously promote the restoration of pathological lung tissues. 77 Therefore, MSC therapy is considered an alternative option for patients with severe COVID-19.…”