Mesenchymal stromal cell conditioned media for lung disease: a systematic review and meta-analysis of preclinical studies

Abstract

BackgroundInflammation plays an important role in the pathogenesis of many lung diseases. Preclinical studies suggest that mesenchymal stromal cell (MSC) conditioned media (CdM) can attenuate inflammation. Our aim was threefold: (1) summarize the existing animal literature evaluating CdM as a therapeutic agent for pediatric/adult lung disease, (2) quantify the effects of CdM on inflammation, and (3) compare inflammatory effects of CdM to MSCs.MethodsAdhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed in five databases. Meta-analysis and meta-regression were performed to generate random effect size using standardized mean difference (SMD).ResultsA total of 10 studies met inclusion. Lung diseases included bronchopulmonary dysplasia, asthma, pulmonary hypertension, and acute respiratory distress syndrome. CdM decreased inflammatory cells (1.02 SMD, 95% CI 0.86, 1.18) and cytokines (0.71 SMD, 95% CI 0.59, 0.84). The strongest effect for inflammatory cells was in bronchopulmonary dysplasia (3.74 SMD, 95% CI 3.13, 4.36) while pulmonary hypertension had the greatest reduction in inflammatory cytokine expression (1.44 SMD, 95% CI 1.18, 1.71). Overall, CdM and MSCs had similar anti-inflammatory effects.ConclusionsIn this meta-analysis of animal models recapitulating lung disease, CdM improved inflammation and had an effect size comparable to MSCs. While these findings are encouraging, the risk of bias and heterogeneity limited the strength of our findings.

Effects of mesenchymal stromal cell-conditioned media on measures of lung structure and function: a systematic review and meta-analysis of preclinical studies

“…Remarkably, preclinical studies suggest MSC conditioned media (CdM) may be as restorative as the MSCs themselves [22,23]. We supported this observation in a previous systematic review and meta-analysis demonstrating that CdM is as effective as MSCs in modulating inflammation [24].…”

Novel Strategies to Reduce Pulmonary Hypertension in Infants With Bronchopulmonary Dysplasia

“…Interestingly, the systematic review indicated that, unlike MSCs, their conditioned media do not improve the PH (88). A similar conclusion was drawn from another systematic review of preclinical studies that used MSCconditioned media for various lung diseases (129). Only two studies (89, 90) on experimental BPD met the criteria for inclusion in these analyses.…”

Review of Trials Currently Testing Stem Cells for Treatment of Respiratory Diseases: Facts Known to Date and Possible Applications to COVID-19

“…Emukah et al [72] conducted a systematic review on the effects of mesenchymal stromal cell conditioned media (CdM) on many lung diseases. The findings were enthusiastic because it was demonstrated that CdM improved inflammation and was as effective as MSCs.…”

“…The findings were enthusiastic because it was demonstrated that CdM improved inflammation and was as effective as MSCs. Further studies must be conducted to determine the ideal site of CdM delivery, dosage, and timing of the treatment according to the lung disease [ 72 ]. Zhao et al [ 73 ] also conducted a systematic review and meta-analysis evaluating the safety of cell therapies and the clinical variables critical for these lung disorders.…”