Table 1.
The main characteristics of the studies included in the meta-analysis
| Reference | Design | Age (MSC vs. Control, years) | Gender (male ratio) | Population | Group(dose, treatment duration) | ITT Population | Outcomes | |
|---|---|---|---|---|---|---|---|---|
| MSC | Control | |||||||
| Guoping Zheng [16] | RCT | 66.7 ± 20.4 vs. 69.8 ± 9.1 | 6/6 vs. 5/6 | N = 12 (1:1), adult patients who met the Berlin definition of moderate and severe ARDS | AD MSCs, 1 × 106 cells/kg of body weight, one IV dose | NS | 12 (6 vs. 6) |
Adverse events Oxygenation index, length of hospital stay, ventilator-free days and ICU-free days at day 28, and SP-D, IL-6 or IL-8 levels in serum |
| Michael Matthay [17] | RCT | 55 ± 17 vs. 55 ± 20 | 23/40 vs. 10/20 | N = 60 (2:1), ventilated adult patients with moderate-to-severe ARDS | BM-MSCs, 10 × 106 MSC/kg (pbw), one IV dose | Placebo | 60 (40 vs. 20) |
Infusion-associated adverse events All-cause mortality, ventilator-free days, intensive-care-free days, days free from organ failure, SOFA score, oxygenation index, and lung injury score Angiopoietin 2, RAGE, IL-6, or IL-8 levels in serum |
| Giacomo Lanzoni [18] | RCT | 58.58 ± 15.93 vs. 58.83 ± 11.61 | 5/12 vs. 8/12 | N = 24 (1:1), adult patients hospitalized for severe COVID-19 |
UC-MSCs, 100 ± 20 × 106 UC-MSCs, 2 IV doses |
50 mL vehicle solution | 24 (12 vs. 12) | Infusion-associated adverse events, cardiac arrest or death within 24 h post-infusion, and incidence of AEs. Survival, time to recovery, and AEs within 31 days |
| Ismail Dilogo [19] | RCT | – | 15/20 vs. 15/20 | N = 40 (1:1), intubated patients with severe COVID-19 (moderate and severe ARDS) | UC-MSCs, 1 × 106 cells/kg body weight, one IV dose | 100 ml NS | 40 (20 vs. 20) |
Mortality rate, length of ventilation, Length of ICU stay, AE or serious AE (SAE) Routine blood count, differential count, CRP, D-dimer, fibrinogen, and procalcitonin, VEGF, ferritin, IL-6, LIF, CX-CR3 in serum |
| G Adas [33] | RCT | – | – | N = 20 (1:1), COVID-19 patients with severe ARDS | WJ MSCs, 3 × 106 cells/kg body weight, three IV doses | Placebo | 20 (10 vs. 10) | Adverse events, mortality, lymphocyte subgroups, and inflammation markers such as CRP, PCT, and Ferritin |
| Antoine Monsel [34] | RCT | 64 ± 10.4 vs. 63.2 ± 11.4 | 17/21 vs. 20/24 | N = 45, COVID-19 patients with ARDS | UC-MSCs, 3 × 106 cells/kg body weight, IV | 150 ml NS | 45 (21 vs. 24) | Respiratory improvement, SOFA scores, PaO2/FiO2 ratios, ventilation-free days and 28-day mortality; adverse events; and inflammatory biomarkers |
| Carmen Rebelatto [35] | RCT | 53 ± 15.3 vs. 61.7 ± 9.7 | 8/11 vs. 4/6 | N = 17, COVID-19 patients with moderate/severe ARDS | UC-MSCs, 5 × 106 cells/kg body weight, IV | Placebo | 17 (11 vs. 6) | Adverse events, mortality, PaO2/FiO2; ferritin, IL-6, CRP, D-dimer, and neutrophils |
| Hamid Aghayan [36] | RCT | 62.3 vs. 58.4 | 6/10 vs. 8/10 | N = 20 (1:1), COVID-19 patients with ARDS | PL-MSCs, 1 × 106 cells/kg body weight, IV | Placebo | 20 (10 vs. 10) | Adverse events, mortality, and lymphocyte subgroups |
| Lei Shi [32] | RCT | 60.72 ± 9.14 vs. 59.94 ± 7.79 | 37/65 vs. 19/35 | N = 100, COVID-19 patients with ARDS | UC-MSCs, 4 × 106 cells/kg body weight, IV | Placebo | 100 (65 vs. 35) | The proportion of whole lung lesion volumes, adverse events, and mortality |
| Lei Shu [37] | RCT | 61.00 ± 17.87 vs. 57.86 ± 15.79 | 8/12 vs. 16/29 | N = 41, COVID-19 patients with ARDS | UC-MSCs, 2 × 106 cells/kg body weight, IV | 100 ml NS | 41 (12 vs. 29) | Mortality, the time to clinical improvement, adverse events, and lab indexes |
| Michael Bowdish [38] | RCT | 61.8 ± 13.0 vs. 59.6 ± 13.8 | 79/112 vs. 75/110 | N = 222, COVID-19 patients with moderate/severe ARDS | BM-MSCs, 2 × 106 cells/kg body weight, IV | Placebo | 222 (112 vs. 110) | Mortality, mechanical ventilation days, clinical improvement, ICU length of stay, and adverse events |
| Najmeh Farkhad [39] | RCT | – | 7/10 vs. 6/10 | N = 20, COVID-19 patients with mild/moderate ARDS | UC-MSCs, 1 × 106 cells/kg body weight, IV | Placebo | 20 (10 vs. 10) | Mortality, PaO2/FiO2, lung imaging, and inflammatory biomarkers such as IL-1 beta, IL-6, and TNF-a |
| Xiaowei Xu [40] | RCT | 58.31 ± 12.49 vs. 61.11 ± 11.03 | 17/26 vs. 13/18 | N = 44, COVID-19 patients with ARDS | UC-MSCs, 9 × 106 cells/kg body weight, IV | Placebo | 44 (26 vs. 18) | Mortality, clinical improvement, PaO2/FiO2, inflammatory indices (including CRP and IL-6), and adverse events |
ITT Intention to treat; AD MSCs Adipose-derived MSCs; BM-MSCs Bone Marrow MSCs; UC-MSCs Umbilical cord MSCs; IV Intravenous; SOFA Sequential Organ Failure Assessment; NS Normal saline; COVID-19 Coronavirus disease 2019