Table 2.
Randomized Clinical Trials of Mesenchymal Stromal Cell Therapies in Patients with Coronavirus Disease Acute Respiratory Failure/Acute Respiratory Distress Syndrome
| Number of Patients |
Patient Population | MSC Therapy Regimen |
Design | Steroid Use | Biological Signal | Adverse Events (n) |
Mortality [n (%)]* |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Therapy | Control | Cell Source | Dose Size | Number of Doses | Treatment | Control | Treatment | Control | |||||
| Cell therapy trials | |||||||||||||
| Shu et al. (2020) (40) | 12 | 29 | Early COVID-19 ARF Not invasive MV (PFR ⩽ 300 mm Hg) |
Umbilical-cord MSCs | 2 × 106 cells/kg | 1 | Placebo control | Yes | Yes (cytokines) | 0† | 0† | 0/12 (0) | 3/29 (10) |
| Adas et al. (2021) (41) | 10 | 10 | Early “severe” COVID-19; invasive MV | Umbilical-cord MSCs | 3 × 106 cells/kg | 3 (D0, D3, D6) | Placebo control | Yes (“per needed”) | Yes (cytokines) | 0† | 0† | 3/10 (30) | 6/10 (60) |
| Dilogo et al. (2021) (42) | 20 | 20 | Early COVID-19 ARF Invasive MV (PFR < 300 mm Hg) Multiorgan failure |
Umbilical-cord MSCs | 1 × 106 cells/kg | 1 | Placebo control | No | Yes (cytokines) | 0† | 0† | 10/20 (50) | 16/20 (80) |
| Shi et al. (2021) (43) | 65 | 35 | Early COVID-19 ARF Not invasive MV (PFR < 300 mm Hg) |
Umbilical-cord MSCs | 4 × 107 cells | 3 (D0, D3, D6) | Placebo control | 20–25% | Yes (lung lesion on CT) | 0†/37‡ | 0†/21‡ | 0/65 (0) | 0/35 (0) |
| Lanzoni et al. (2022) (44) | 12 | 12 | Early COVID-19 ARF Advanced respiratory support including invasive MV (PFR < 300 mm Hg) |
Umbilical-cord MSCs | 1 × 108 cells | 2 (D0, D3) | Placebo control | Yes (80%) | Yes (cytokines) | 1†/35‡ | 1†/53‡ | 1/12 (8) | 7/12 (58) |
| Monsel et al. (2022) (16) | 21 | 24 | Early COVID-19 ARDS Advanced respiratory support including invasive MV (PFR < 300 mm Hg |
Umbilical-cord MSCs | 1 × 106 cells/kg | 3 (D0, D3, D5) | Placebo control | Yes (75%) | Yes (cytokines) | 1†/49‡ | 0†/48‡ | 5/21 (24) | 4/24 (17) |
| Rebelatto et al. (2022) (45) | 11 | 6 | Early ARDS; invasive MV (PFR ⩽ 300 mm Hg) | Umbilical-cord MSCs | 5 × 105 cells/kg | 3 (D0, D3, D5) | Placebo control | Yes (100%) | Yes (cytokines) | 0† | 0† | 5/11 (45) | 1/6 (17) |
| Bowdish et al. (2023) (15) | 112 | 110 | Early ARDS; invasive MV (PFR ⩽ 200 mm Hg) | BM | 2 × 106 cells/kg | 2 (D1, D4) | Placebo control | Yes | Not reported | 0†/167‡ | 0†/153‡ | 42/112 (37.5) | 47/110 (42.7) |
| Gorman et al. (2023) (17) | 30 | 29 | Early ARDS; invasive MV (PFR ⩽ 200 mm Hg) | Umbilical cord | 4 × 108 cells | 1 | Placebo control | Yes | Yes (transcriptome) | 6 | 3 | 7/30 (23) | 8/31 (26) |
| Cell products trials | |||||||||||||
| Fathi-Kazerooni et al. (2002) (46) | 14 | 15 | Early COVID-19 ARF Advanced respiratory support including invasive MV (PFR < 300 mm Hg) |
Menstrual blood MSC | Secretome 5ml | 5 (D0–D4) | Placebo control | 100% | Yes (CRP; D-dimer) | 0† | 0† | 6/14 (43) | 12/15 (80) |
| Lightner et al. (2023) (18) | EF-15: n = 34 EF-10: n = 34 |
34 | Early COVID-19 ARF Advanced respiratory support including invasive MV (PFR < 300 mm Hg) |
BM-MSC–derived EVs | EF-15: 15 ml EF-10: 10 ml |
1 | Placebo control | 100% | Not reported | EF-15: 0†/24‡ EF-10: 0†/26‡ |
1†/23‡ | EF-15: 10 EF-10: 14 |
16/34 (47) |
Definition of abbreviations: ARDS = acute respiratory distress syndrome; ARF = acute respiratory failure; BM = bone marrow; CRP = C-reactive protein; CT = computed tomography; D = day; EF-10 = ExoFlo (10 ml); EF-15 = ExoFlo (15 ml); EV = extracellular vesicle; MSC = mesenchymal stromal cell; MV = mechanical ventilation; PFR = PaO2:FiO2 ratio.
*
Mortality at the latest time point reported in the study.
†
Only adverse events possible/likely/related to therapy reported.
‡
Total number of adverse events (some patients had more than one adverse event).