Abstract
BackgroundThe investigation of mesenchymal stromal cell (MSC)-conditioned medium or extracellular vesicles (exosomes or microvesicles) as a remedy for acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) has become a fast-growing field in recent years. Our purpose was to conduct a meta-analysis to investigate the efficacy of MSC-derived therapies (MDTs) for ALI/ARDS in animal models.MethodsA meta-analysis of MDTs for ALI/ARDS in animal trials was performed. PubMed and EMBASE were searched to screen relevant preclinical trials with a predetermined search strategy.ResultsA total of 17 studies that compared MDT with the ALI control group were included in our study. The pooled result derived from the comparison of the two groups suggested that MDT could significantly reduce the lung injury score (standardized mean difference (SMD) = − 4.02, 95% CI [− 5.28, − 2.23], P < 0.0001) and improve animal survival (OR = − 6.45, 95% CI [2.78, 14.97], P < 0.0001). MDT mitigated the infiltration of neutrophils in alveoli (SMD = − 3.38, 95% CI [− 4.58, − 2.18], P < 0.00001). MDT also reduced the wet-dry weight ratio of the lung (SMD = − 2.34, 95% CI [− 3.42, − 1.26], P < 0.0001) and the total protein in BALF (SMD = − 2.23, 95% CI [− 3.07, − 1.40], P < 0.00001). Furthermore, MDT was found to downregulate proinflammatory mediators such as IL-1, IL-6 and TNF-a and to upregulate anti-inflammatory mediators such as IL-10.ConclusionMDT reduces lung injury and improves survival in animal ARDS models since it can ameliorate lung permeability, decrease inflammatory cell infiltration, downregulate proinflammatory mediators, and upregulate anti-inflammatory mediators. However, more animal studies and human trials are needed for further investigation.
Highlights
In critically ill patients, acute respiratory distress syndrome (ARDS) is a severe clinical syndrome with high morbidity and mortality [1]
Mesenchymal stromal cells (MSCs) may be effective for acute lung injury (ALI)/ARDS caused by a variety of pathogenic factors, as they can ameliorate lung permeability, decrease inflammatory cell infiltration, downregulate inflammatory mediators and upregulate anti-inflammatory mediators
SD Sprague–Dawley, LPS lipopolysaccharide, CFU colony forming unit, IP intra-peritoneal, IT intratracheal, IV intravenous, Bone marrow (BM) bone marrow, Umbilical cord (UC) umbilical cord, AD adipose-derived, MSC mesenchymal stromal cells, conditioned medium (CM) conditoned medium control group, indicated that MSC-derived therapies (MDTs) can significantly promote animal survival, with an odds ratios (ORs) = − 6.45, 95% CI [2.78, 14.97], P < 0.0001, and I2 = 2% (Fig. 2b)
Summary
ARDS is a severe clinical syndrome with high morbidity and mortality [1]. Immunomodulatory, and tissue and organ repair and regeneration characteristics, MSCs have been widely investigated as a potential therapy in different scenarios for ALI/ARDS in the last few decades [6]. We will investigate the efficacy of MDT for ALI/ARDS to evaluate whether it can improve survival, lower lung injury severity, and regulate immune balance via a meta-analysis of animal models. The investigation of mesenchymal stromal cell (MSC)-conditioned medium or extracellular vesicles (exosomes or microvesicles) as a remedy for acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) has become a fast-growing field in recent years. Our purpose was to conduct a meta-analysis to investigate the efficacy of MSC-derived therapies (MDTs) for ALI/ARDS in animal models
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