Table 1.
Summarisation of clinical studies and ongoing clinical trials assessing the therapeutic benefit of MSC transplantation in patients with COVID-19, including studies assessing the therapeutic potential of MSCs in patients with acute respiratory distress syndrome (ARDS), without COVID-19.
| Citation | N | Subjects | MSC source and dose | MSC timing | Recipient site | Results |
|---|---|---|---|---|---|---|
| Leng et al. (133) | MSC transplant: n = 7; CON: n = 3 | COVID-19 pneumonia | Clinical grade ACE2− MSCs at 1 × 106 cells/kg | The time when symptoms and/or signs were still getting worse, even as the expectant treatments were being conducted | Systemic | - ↑ IL-10 vs. CON - ↓ TNF-α vs. CON - ↔ IP-10 - Trend for ↑ VEGF vs. CON - Inflammation, AAT, MYO and CK reduced in critically severe patient with a reduction in ground-glass opacity and pneumonia infiltration |
| Liang et al. (161) | Case study | Critical COVID-19 | Allogenic hUCMSCs at 5 × 107 cells 3 times | Admitted 2 days after symptoms onset and MSCs were transplanted on the 9, 12, and 15th days after admission. In combination with antibiotics and thymosin α1 | Systemic | No side effects were observed. After 2nd administration: - ↓ Bilirubin, WBC and neutrophil count, CRP and ALT/AST - ↑ lymphocyte count - ↑ CD3+, CD4+, and CD8+ T cells - Trachea cannula removed After 3rd administration: - Pneumonia relieved - Removed from ICU 2 days following - Negative throat swab |
| Zhang et al. (162) | Case study | COVID-19 pneumonia - History of diabetes | Wharton's jelly-derived hUCMSCs at 1 x 106 cells/kg | Admitted 5 days after symptoms onset and MSCs were transplanted on the 17th day of admission | Systemic | Post-transplant: - COVID-19 symptoms disappeared 2 to 7 days - ↓ Ground glass opacity and pneumonia infiltration day 6 - ↑ CD3+, CD4+ & CD8+ T cells - ↓ CRP, IL-6 & TNF-α |
| Chen et al. (163) | MSC transplant: n = 17; CON: n = 44 | H7N9-induced ARDS | Allogenic menstrual-blood-derived MSCs at 1 × 106 cells/kg | 3 patients treated with 3 infusion at the early stage of infection; 6 patients were treated with 3 infusions at the late stage of infection; 8 patients accepted 4 infusions of at late stage of infection | Systemic | At admission: - No differences, except ↓ PCT vs. CON At discharge: - ↑ mortality rate of CON - ↓ PCT, ALT, sCr, CK, PT, and D-dimer vs. CON At follow-up (5 year; n = 4): - ↑ Hb - ↓ PT |
| Sengupta et al. (164) | N = 23 | COVID-19: cohort a (mild COVID-19): n = 1; cohort b (hypoxaemia and COVID-19): n = 20; cohort c (intubated COVID-19): n = 3 | Bone-marrow derived MSCs exosome agent—ExoFlow-−15 mL | Not specified | Systemic | −71% patients recovered and/or were discharged after 5.6 days post-infusion - 13% remained critically ill - 16% died - 80% improved PaO2/FiO2 ratio within 3 days - ↓ CRP, ferritin and D-dimer on day 5 -↑ CD3+, CD4+, and CD8+ T cells on day 5 |
CON, control; ACE2, Angiotensin converting enzyme 2; IL-10, Interleukin-10; TNF-α, Tumor necrosis factor α; IP-10, Interferon gamma-induced protein 10; VEGF, Vascular endothelial growth factor; AST, Aspartate amino transferase; MYO, Myoglobin; CK, Creatine kinase; hUCMSC, human umbilical cord mesenchymal stem cells; WBC, white blood cell; CRP, C-reactive protein; ALT, Alanine aminotransferase; ICU, intensive care unit; ARDS, Acute respiratory distress syndrome; PCT, Procalcitonin; sCr, serum creatinine; PT, Prothrombin time.