Living bio-drug therapies using mesenchymal stem cells and exosomes for mechanically ventilated patients with acute respiratory distress syndrome: A systematic review and meta-analysis

Figure 1 Study selection flow diagram (PRISMA chart). RCT: Randomized controlled trial; MSCs: Mesenchymal stem cells; ARDS: Acute respiratory distress syndrome.

Figure 2 The quality assessment of the included trials based on the Cochrane risk of bias tool 1. D: Domain.

Figure 3 Forest plots showing duration of mechanical ventilation and ventilation-free days in patients treated with mesenchymal stem cells vs control. A: Forest plots showing duration of mechanical ventilation in patients treated with mesenchymal stem cells vs control; B: Forest plots showing ventilation-free days in patients treated with mesenchymal stem cells vs control. The pooled weighted mean difference, along with its 95% confidence interval, is presented. Each square represents the effect estimate of an individual study, with the size proportional to its weight in the meta-analysis; horizontal lines denote the 95% confidence interval. The diamond indicates the overall pooled effect. MSC: Mesenchymal stem cell; CI: Confidence interval.

Figure 4 Forest plot showing length of hospital stay, length of intensive care unit stay, and 6-minute walk distance test to determine the change in patients treated with mesenchymal stem cells vs the control. A: Forest plot showing length of hospital stay to determine the change in patients treated with mesenchymal stem cells (MSCs) vs the control; B: Forest plot showing length of intensive care unit stay to determine the change in patients treated with MSCs vs the control; C: Forest plot showing 6-minute walk distance test to determine the change in patients treated with MSCs vs the control. The pooled weighted mean difference, along with its 95% confidence interval, is presented. Each square represents the effect estimate of an individual study, with the size proportional to its weight in the meta-analysis; horizontal lines denote the 95% confidence interval. The diamond indicates the overall pooled effect. MSC: Mesenchymal stem cell; CI: Confidence interval.

Figure 5 Forest plot showing the effect of mesenchymal stem cells and exosomes on mortality and odds ratio of adverse events. A: Forest plot showing the effect of mesenchymal stem cells and exosomes on mortality rates; B: Forest plot showing the effect of mesenchymal stem cells and exosomes on the odds ratio of adverse events. The pooled odds ratio, along with its 95% confidence interval, is presented. Each square represents the effect estimate of an individual study, with the size proportional to its weight in the meta-analysis; horizontal lines denote the 95% confidence interval. The diamond indicates the overall pooled effect. MSC: Mesenchymal stem cell; CI: Confidence interval.

Figure 6 Network graphs of the effect of different treatment arms on mechanical ventilation-free days, mortality, and adverse events. A: Network graphs of the effect of different treatment arms on adverse events; B: Network graphs of the effect of different treatment arms on mechanical ventilation-free days; C: Network graphs of the effect of different treatment arms on mortality. MSC: Mesenchymal stem cell.

Figure 7 Network meta-analysis comparing exosomes and mesenchymal stem cells vs control interventions. A-C: Forest plots showing mechanical ventilation-free days (mean difference) (A), mortality (odds ratio) (B), and adverse events (odds ratio) (C). Each panel displays direct estimates, indirect estimates, and network estimates, along with 95% confidence intervals. The analysis includes three treatment comparisons: Exosomes vs control, mesenchymal stem cells vs control, and exosomes vs mesenchymal stem cells. Numbers indicate the number of studies contributing to each comparison, with I² values representing the level of heterogeneity. MD: Mean difference; OR: Odds ratio; CI: Confidence interval.

Figure 8 The surface under the cumulative ranking curve probability of the ranking plot for the effect of different treatment arms on mechanical ventilation free days, mortality, and adverse events. A: The surface under the cumulative ranking curve probability of the ranking plot for the effect of different treatment arms on mechanical ventilation free days; B: The surface under the cumulative ranking curve probability of the ranking plot for the effect of different treatment arms on mortality; C: The surface under the cumulative ranking curve probability of the ranking plot for the effect of different treatment arms on adverse events. MSC: Mesenchymal stem cell.