Mesenchymal Stromal Cells Attenuate Infection-Induced Acute Respiratory Distress Syndrome in Animal Experiments: A Meta-Analysis

Abstract

Mesenchymal stromal cell (MSC) therapy is a potential therapy for treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which was widely studied in the last decade. The purpose of our meta-analysis was to investigate the efficacy of MSCs for simulated infection-induced ALI/ARDS in animal trials. PubMed and EMBASE were searched to screen relevant preclinical trials with a prespecified search strategy. 57 studies met the inclusion criteria and were included in our study. Our meta-analysis showed that MSCs can reduce the lung injury score of ALI caused by lipopolysaccharide or bacteria (standardized mean difference (SMD) = -2.97, 95% CI [-3.64 to -2.30], P < 0.00001) and improve the animals' survival (odds ratio = 3.64, 95% CI [2.55 to 5.19], P < 0.00001). Our study discovered that MSCs can reduce the wet weight to dry weight ratio of the lung (SMD = -2.58, 95% CI [-3.24 to -1.91], P < 0.00001). The proportion of the alveolar sac in the MSC group was higher than that in the control group (SMD = 1.68, 95% CI [1.22 to 2.13], P < 0.00001). Moreover, our study detected that MSCs can downregulate the levels of proinflammatory factors such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the lung and it can upregulate the level of anti-inflammatory factor IL-10. MSCs were also found to reduce the level of neutrophils and total protein in bronchoalveolar lavage fluid, decrease myeloperoxidase (MPO) activity in the lung, and improve lung compliance. MSC therapy may be a promising treatment for ALI/ARDS since it may mitigate the severity of lung injury, modulate the immune balance, and ameliorate the permeability of lung vessels in ALI/ARDS, thus facilitating lung regeneration and repair.

Keywords: acute lung injury; acute respiratory distress syndrome; cell therapy; mesenchymal stromal cell; stem cell.

Figure 1.

Study flow diagram for selecting relevant preclinical trials.

Figure 2.

Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included studies.

Figure 3.

Main outcomes meta-analyses of MSCs comparing with ALI control group: (a) lung injury score; (b) lung injury score subgroup; and (c) survival. The size of each square represents the proportion of information given by each trial. Crossing with the vertical line suggests no difference between the two groups. ALI: acute lung injury; MSCs: mesenchymal stem cells.

Figure 4.

The meta-analyses of inflammatory and anti-inflammatory factors compare MSCs with ALI control group: (a) IL-1β, (b) IL-6, (c) TNF-α, and (d) IL-10. The size of each square represents the proportion of information given by each trial. Crossing with the vertical line suggests no difference between the two groups. ALI: acute lung injury; IL: interleukin; TNF-α: tumor necrosis factor-α; MSCs: mesenchymal stem cells.

Figure 5.

The meta-analyses of (a) W/D ratio, (b) alveolar sac percentage, (c) total protein, and (d) neutrophils in BALF compare MSCs with the ALI control group. The size of each square represents the proportion of information given by each trial. Crossing with the vertical line suggests no difference between the two groups. ALI: acute lung injury; BALF: bronchoalveolar lavage fluid; MSCs: mesenchymal stem cells; W/D: wet to dry ratio.

Figure 6.

The meta-analyses of (a) PaO₂, (b) lung compliance, and (c) MPO activity in lung compare MSCs with the ALI control group. The size of each square represents the proportion of information given by each trial. Crossing with the vertical line suggests no difference between the two groups. ALI: acute lung injury; MPO: myeloperoxidase; MSCs: mesenchymal stem cells; PaO₂: partial pressure of oxygen.