| MSCs source/ number of patients | Severity of the disease | Administration method/dose | Study design/ Intervention model | Concomitant treatment | Outcomes | Adverse events | References |
| Umbilical/ Cord/47 |
| Intravenous, 3 cycles; 1 × 106 cells/Kg | Multicentre, double-blind, randomized, placebo-controlled trial. | None | No improvement in survival rate and no PaO2/FiO2 changes between D0 and D7. | None related to MSCs treatment | [163] |
| Umbilical cord/1 | Severe | Intravenous, 3 cycles; 1 × 106 cells/Kg | None | Convalescent plasma | Inhibiting cytokine storm, promoting the repair of lung injury, and recovering pulmonary function. | None reported | [164] |
| Umbilical cord/16 | Severe and critically ill | Intravenous, 4 cycles; 1 × 108 cells. | Non-randomized | None | Improvement of oxygenation index and in lymphocytes counts, and decrease in pro-inflammatory cytokines levels (IL-1, IL-6, IFN-γ, TNF-α). | None reported | [142] |
| Umbilical cord/31 | Severe or critical | Intravenous, 1 - 3 cycles; 1 × 106 cells/Kg. | Non-randomized | Antibiotics, antivirals, and intravenous immunoglobulin. | Increase in lymphocytes count, decrease in IL-6 and CRP concentrations, and SARS-CoV-2 PCR negative after 10.7 days. | None reported | [165] |
| Umbilical cord/100 | Severe | Intravenous, 3 cycles; 4 × 107 cells. | Randomized, double-blind, and placebo-controlled | None | Decrease in the size of lesion and severity of pulmonary fibrosis by chest CT and improvement in pneumonia and oxygenation. | Reported but no details | [166] |
| Adipose tissue/13 | Severe | Intravenous, 3 cycles; 1 × 106/Kg. | Non-randomized | None | Reduction in CRP, lactate dehydrogenase (LDH), D-dimer and ferritin and increase in B and CD4+ /CD8+T-lymphocyte counts. | None reported | [82] |
| Umbilical cord/1 | Critically ill | Intravenous, 3 cycles; 5 × 107 cells. | Non-randomized | Thymosin α1 and antibiotics. | The counts of CD3+ T cell, CD4+ T cell, and CD8+ T cell remarkably increased to the normal level, pulmonary. Inflammatory reaction was greatly alleviated. Good clinical outcome and good tolerance of allogenic transfer. Transfer out of ICU, and SARS-CoV-2 negative test after 4 days. | None reported | [81] |
| Not reported/7 | 1 critically severe, 4 severe, and 2 moderate | Intravenous, 1 dose 1 × 106 cells/Kg. | Non-randomized | None | The respiratory rate was regulated 4 days after MSCs transplantation. Both fever and tightness of breath disappeared. The plasma C-reaction protein level decreased. The lymphopenia was significantly improved. Overactivated T cells and NK cells nearly disappeared, and the numbers of the other cell subpopulations were almost restored to the normal levels, especially the CD14 + CD11c + CD11bmid regulatory dendritic cell population. The serum pro-inflammatory cytokine TNF-α was reduced. The serum levels of chemokines like IL-10 and growth factor VEGF were both increased. | None reported | [14] |
| Umbilical cord/18 | Moderate and severe | Intravenous, 3 cycles; 3 × 107 cells per infusion. | Non-randomized | None | IL-6 exhibited a decline within 3 days. Reduced trend in the levels of IFN-γ, TNF-α, MCP-1, IL-22, IL-1RA, IL-18, IL-8, and MIP-1 within 14 days. CT scans indicated that patients showed absorption of pulmonary pathological changes and the lung lesions were well controlled within 6 days, and completely faded away within 2 weeks. Recovery. | Two patients receiving UC-MSCs developed transient facial flushing and fever, and one patient developed transient hypoxemia at 12 h post UC-MSCs transfusion. | [15] |
| Umbilical cord/12 | Severe | Intravenous; 1 dose, 2 × 106 cells/kg | Single-center, open-label, individually randomized trial | Antiviral and antibiotic treatments, glucocorticoid therapy and vasopressors. | The levels of inflammatory factors, including IL-6 and C-reaction protein (CRP), could be rapidly reduced, and the lymphocyte count could return to normal levels in less time. As the patient’s chest tightness and shortness of breath quickly improved, arterial blood gas suggested that the oxygenation index could improve. Chest CT scans demonstrated a reduced lung inflammation. | None reported | [88] |
| Dental pulp/20 | Severe | Intravenous; 3 doses; 3 × 107 | Single center, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group. | None | Good clinical outcome and good tolerance of allogenic transfer. | None reported | [22] |
| Umbilical cord Wharton’s jelly/1 | Severe | Intravenous; 1 dose, 1 × 106 cells/Kg | Non-randomized | Dexamethasone (2 mg) before intravenous infusion. | The percentage and counts of CD3+ T cell, CD4+ T cell, and CD8+ T cell were increased The levels of plasma CRP and inflammatory factors (IL-6 and TNF-α) were all decreased after the umbilical cord wharton’s jelly treatment. Both fever and shortness of breath disappeared on the 2nd day after transplantation. | None reported | [16] |
| Umbilical cord or placental/11 | Critically ill | Intravenous 3 doses, 200 × 106 cells | Non-randomized | Different treatment protocols: hydroxychloroquine, kaletra, azithromycin, ribavarin, favipiravir, vancomycin, colistin. | Significant reductions in serum levels of TNF-a, IL-8, IL-6, IFN-γ and CRP. Four patients who had signs of multi-organ failure or sepsis died in an average of 10 days after the first MSC infusion. | No serious adverse events reported 24 - 48 hours after the cell infusions. Reduced dyspnea was observed One patient showed signs of acute renal and hepatic failure and cardiac arrest development. | [167] |
| Umbilical cord/24 | 6 mild to moderate, and 18 moderate to severe | Intravenous; 2 doses, 100 ± 20 × 106 cells | Double-blind, placebo controlled, randomized trial. | Heparin, remdesivir, corticosteroids, tocilizmab, hydroxychloroquine. | Inflammatory cytokines were significantly decreased in 6 days. Improved patient survival. | New cardia arrhythmia requiring cardioversion. Worsening hypoxemia. | [17] |
| Not specified/23 | Severe | 10 Infusion; 2 to 3, doses, 106 cells/kg | Non-randomized | None | In the MSC group, 80% patients survived to discharge and exhibited good pulmonary function, whereas only 45% of patients in the control group survived to discharge. Decrease of CRP and IL-6. The incidence of kidney injury and hepatic failure in the MSC group did not differ from the incidence in the control group of patients. Patients in the MSC group showed lower mortality than those in the control group (20% vs. 55.6%). | None reported | [168] |
| Umbilical cord blood derived MSCs/1 | Severe | Intravenous 5 doses, 1.5 × 106 per kilogram | Non-randomized | Recombinant human interferon, lopinavir/ritonavir, piperacillin tazobactam and heparin. | Hematological and biochemical indexes, including lymphocytes and renal function improved. Pulmonary static compliance increased significantly and PaO2/FiO2 ratio maintained stable. | None reported | [169] |
| Menstrual blood-derived MSCs/2 | Severe | Intravenous 3 doses, 1 × 106 per kilogram | Non-randomized | Ribavirin, arbidol hydrochloride, oseltamivir, and cefoperazone-sulbactam. | MSC transplantation increases the immune indicators (including CD4 and lymphocytes) and decreases the inflammation indicators (IL-6 and CRP). the fraction of inspired O2 (FiO2) of the two patients gradually decreased while the oxygen saturation (SaO2) and partial pressure of oxygen (PaO2) improved. Chest CT showed that bilateral lung exudate lesions were adsorbed after MSC infusion. | None reported | [170] |