Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS
BACKGROUND Whether airspace biomarkers add value to plasma biomarkers in studying acute respiratory distress syndrome (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...
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-06-01
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| Series: | JCI Insight |
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| Online Access: | https://doi.org/10.1172/jci.insight.148983 |
| _version_ | 1811329106283855872 |
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| author | Katherine D. Wick Aleksandra Leligdowicz Hanjing Zhuo Lorraine B. Ware Michael A. Matthay |
| author_facet | Katherine D. Wick Aleksandra Leligdowicz Hanjing Zhuo Lorraine B. Ware Michael A. Matthay |
| author_sort | Katherine D. Wick |
| collection | DOAJ |
| description | BACKGROUND Whether airspace biomarkers add value to plasma biomarkers in studying acute respiratory distress syndrome (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. Nonbronchoscopic 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 with placebo, MSC treatment significantly reduced airspace total protein, angiopoietin-2 (Ang-2), IL-6, and soluble TNF 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).CONCLUSION 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 ClinicalTrials.gov NCT02097641.FUNDING National Heart, Lung, and Blood Institute. |
| first_indexed | 2024-04-13T15:38:01Z |
| format | Article |
| id | doaj.art-c386153c9b17475ebb8cd432df6342bd |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T15:38:01Z |
| publishDate | 2021-06-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-c386153c9b17475ebb8cd432df6342bd2022-12-22T02:41:13ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-06-01612Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDSKatherine D. WickAleksandra LeligdowiczHanjing ZhuoLorraine B. WareMichael A. MatthayBACKGROUND Whether airspace biomarkers add value to plasma biomarkers in studying acute respiratory distress syndrome (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. Nonbronchoscopic 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 with placebo, MSC treatment significantly reduced airspace total protein, angiopoietin-2 (Ang-2), IL-6, and soluble TNF 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).CONCLUSION 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 ClinicalTrials.gov NCT02097641.FUNDING National Heart, Lung, and Blood Institute.https://doi.org/10.1172/jci.insight.148983PulmonologyStem cells |
| spellingShingle | Katherine D. Wick Aleksandra Leligdowicz Hanjing Zhuo Lorraine B. Ware Michael A. Matthay Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS JCI Insight Pulmonology Stem cells |
| title | Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS |
| title_full | Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS |
| title_fullStr | Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS |
| title_full_unstemmed | Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS |
| title_short | Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS |
| title_sort | mesenchymal stromal cells reduce evidence of lung injury in patients with ards |
| topic | Pulmonology Stem cells |
| url | https://doi.org/10.1172/jci.insight.148983 |
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