Table 1: The clinical trials of MSCs on COVID-19.
Identifier |
Phase |
Status |
Location |
Cell Type |
Estimated Enrollment |
Doses and Route of Administration |
Primary Outcome Measure |
NCT04252118 |
1 |
Recruiting |
China |
Allogeneic UC-MSC |
20 |
Three doses of 3.0 × 107 at days 0, 3, 6 |
Size of lesion area by chest radiograph or CT, Side effects in MSC treatment group |
NCT04276987 |
1 |
Completed |
China |
Allogeneic adipose MSC-exos |
30 |
Five doses of 2.0 × 108 nanovesicles, days 1, 2, 3, 4, and 5, aerosol inhalation route |
Adverse and severe adverse reaction, Time to clinical improvement |
NCT04299152 |
2 |
Not yet recruiting |
China |
CB-MSC |
20 |
N/A |
Number of patients unable to complete SCE therapy |
NCT04273646 |
N/A |
Not yet recruiting |
China |
Allogeneic UC-MSC |
48 |
Four doses of 5.0 × 106 cells/kg at, days 1, 3, 5, and 7, IV+ conventional treatment |
Pneumonia severity index, Oxygenation index |
NCT04288102 |
1-2 |
Completed |
China |
Allogeneic UC-MSC |
90 (Placebo:30) |
Three doses of 4 × 107, at days 0, 3, 6, IV + standard of care |
Size of lesion area and severity of pulmonary fibrosis by CT |
NCT04302519 |
1 |
Not yet recruiting |
Shanghai |
Dental pulp MSC |
24 |
Three doses of 1.0 × 106 cells/kg, at days 1, 3, and 7, IV |
Disappear time of ground-glass shadow in the lungs |
NCT04313322 |
1 |
Recruiting |
Jordan |
Allogeneic WJ-MSC |
5 |
Three doses of 1 × 106/kg, 3 days apart, IV |
Clinical outcome, CT scan, RT-PCR results |
NCT04293692 |
N/A |
Withdrawn |
China |
UC-MSC |
N/A |
Study was withdrawn before participants were enrolled. |
Size of lesion area by chest imaging, Blood oxygen saturation |
NCT04269525 |
2 |
Recruiting |
China |
Allogeneic UC-MSC |
10 |
Four doses of 3.3 × 107 cells at, days 1, 3, 5, and 7, IV |
Oxygenation index |
NCT04457609 |
1 |
Recruiting |
Indonesia |
UC-MSC |
40 |
Intravenous infusion of 1 × 106 unit of UC- MSCs/kg BW in 100 cc of 0.9% NaCl for 1 h, in addition to standardized treatment (oseltamivir and azithromycin) |
Presence of dyspnea, presence of sputum, fever, ventilation status, blood pressure, heart rate, respiratory rate, oxygen saturation |
NCT04461925 |
1-2 |
Recruiting |
Ukraine |
Allogeneic placenta MSC |
30 |
1 million cells/kg body weight/time, once every 3 days for a total of 3 times: day “1”, day “4”, day “7”, IV + ceftriaxone, azithromycin, anticoagulants, hormones, oxygen therapy, mechanical ventilation and other supportive therapies |
Changes of oxygenation index PaO2/FiO2, most conveniently the P/F ratio. Changes in length of hospital stay, Changes in mortality rate |
NCT04466098 |
2 |
Not yet recruiting |
N/A |
MSC |
30 (Placebo:15) |
300 × 106 MSCs, three fixed doses of MSCs, approximately 48 h apart, IV |
Incidence of grade 3-5 infusional toxicities and predefned hemodynamic or respiratory adverse events related to the infusion of MSC |
NCT04416139 |
2 |
Recruiting |
Mexico |
UC-MSC |
10 |
1 million/kg in a single dose, IV |
Functional respiratory changes: PaO2/FiO2 ratio, Clinical cardiac changes: Heart rate per minute, Clinical respiratory changes: respiratory rate per minute, Changes in body temperature |
NCT04336254 |
1-2 |
Recruiting |
China |
Allogeneic dental pulp MSC |
20 |
Three doses of 3.0 × 107 cells/dose at, days 1, 4 and 7, IV |
Time to clinical improvement |
NCT04429763 |
2 |
Not yet recruiting |
Colombia |
UC-MSC |
30 |
1 × 106 cells/kg single dose, IV |
Clinical deterioration or death |
NCT04456361 |
1 |
Active, not recruiting |
N/A |
WJ-UC-MSC |
9 |
Single-dose of 1 × 108 cells, IV |
Oxygen saturation |
NCT04315987 |
2 |
Not yet recruiting |
Brazil |
MSC |
90 (Placebo:45) |
Four doses of 2 × 106/kg, at days 1, 3, 5, and 7, IV |
Change in clinical condition |
NCT04366063 |
2-3 |
Recruiting |
Iran |
MSC |
60 (Placebo:20) |
Intervention group 1: two doses 1 × 108 at day 0, 2, IV Intervention group 2: two doses 1 × 108 at day 0, 2 + EVs at days 4, 6, IV |
Adverse events assessment, Blood oxygen saturation |
NCT04437823 |
2 |
Recruiting |
Pakistan |
UC-MSC |
20 (Placebo:5) |
5 × 105 UCMSCs per kg, IV on days 1, 3 and 5 besides the standard care (SOC) |
Safety and efficacy assessment of infusion associated adverse events, Chest radiograph or Chest CT scan |
NCT04390152 |
1-2 |
Not yet recruiting |
Colombia |
Allogeneic WJ-MSC |
40 |
Two doses of 50 × 106, IV |
Intergroup mortality diference with treatment |
NCT04339660 |
1-2 |
Recruiting |
China |
Allogeneic UC-MSC |
30 |
One-two doses of 1 × 106/kg (1 week apart), IV |
The immune function, Blood oxygen saturation |
NCT04392778 |
1-2 |
Recruiting |
Turkey |
Allogeneic UC-MSC |
30 (Placebo:20) |
Three doses of 3 × 106 cells/kg on days 0, 3, and 6, IV |
Clinical improvement |
NCT04355728 |
1-2 |
Recruiting |
United States |
Allogeneic UC-MSC |
24 (Placebo:12) |
Two doses of 100 × 106 cells, IV |
Incidence of pre-specifed infusion-associated adverse events, Incidence of Severe Adverse Events |
NCT04371601 |
1 |
Active, not recruiting |
China |
Allogeneic UC-MSC |
60 |
Four single doses of 1 × 106/kg, 4 days apart, IV + Oseltamivir |
Changes of oxygenation index, blood gas test |
NCT04393415 |
N/A |
Not yet recruiting |
Egypt |
Allogeneic UC-MSC |
100 |
UC-MSC (undefined dose) + platelet rich plasma (PRP) |
The number of patients with positive covid 19 who will improve after receiving stem cells |
NCT04452097 |
1 |
Not yet recruiting |
NA |
UC-MSC |
39 (Placebo:12) |
0.5 million cells/kg, IV, plus standard treatment |
Incidence of infusion-related adverse events, Incidence of any treatment-emergent adverse events and treatment emergent serious adverse events |
NCT04390139 |
1-2 |
Recruiting |
Spain |
WJ-MSC |
30 |
Two doses, 1 × 106 cells/kg, IV |
All-cause mortality at day 28 |
NCT04333368 |
1-2 |
Recruiting |
France |
Allogeneic WJ-UC-MSC |
40 (Placebo:20) |
Three doses of 1.0 × 106 cells/kg at days 1, 3, and 5, IV |
Respiratory efcacy evaluated by the increase in PaO2/FiO2 ratio from baseline to day 7 in the experimental group compared with the placebo group |
NCT04565665 |
1 |
N/A |
United States |
CB-MSC |
70 |
N/A |
Incidence of composite serious adverse events (Phase I), Patients alive without grade 3, 4 infusional toxicity (Phase II), Patients alive with grade 3 or 4 infusional toxicity (Phase II), Patients not alive (Phase II) |
NCT04377334 |
2 |
Not yet recruiting |
Germany |
Allogeneic BM-MSC |
40 |
N/A |
Improvement of lung injury score (LIS), 0-16 points, severity increasing with higher points |
NCT04467047 |
1 |
Not yet recruiting |
Brazil |
Allogeneic BM-MSC |
10 |
1 × 106 MSCs/kg, IV |
Overall survival |
NCT04444271 |
2 |
Recruiting |
Pakistan |
Autologous BM-MSC |
20 (Placebo:10) |
2 × 106 cells/kg on days 1 and 7 (if needed), IV |
Overall survival |
NCT04366323 |
1-2 |
Recruiting |
Spain |
Allogeneic adipose MSC |
26 |
Two doses of 8 × 107 cell/dose, IV |
Safety of the administration of allogeneic mesenchymal stem cells derived from adipose tissue, Efficacy of the administration of allogeneic mesenchymal stem cells derived from adipose tissue |
NCT04348435 |
2 |
Enrolling by invitation |
United States |
Allogeneic adipose MSC |
100 (Placebo:25) |
Five doses of either 2 × 108, 1 × 108 or 5 × 107 cells/single doses at weeks 0, 2, 6, 10, and 14, IV |
Incidence of hospitalization for COVID-19, Incidence of symptoms associated with COVID-19 |
NCT04382547 |
1-2 |
Enrolling by invitation |
Belarus |
Allogeneic mucosa MSC |
40 |
Dose unspecified, IV |
Number of cured patients |
NCT04349631 |
2 |
Enrolling by invitation |
United States |
Autologous adipose MSC |
56 |
Five doses of cells (unspecified dose), IV |
Incidence of hospitalization for COVID-19, Incidence of symptoms for COVID-19 |
NCT04346368 |
1-2 |
Not yet recruiting |
China |
BM-MSC |
20 |
Single dose 1 × 106 MSCs/kg, IV |
Changes of oxygenation index (PaO2/FiO2), Side efects in the BM-MSC treatment group |
NCT04447833 |
1 |
Recruiting |
N/A |
Allogeneic BM-MSC |
9 |
First three patients receive a single dose of 1 × 106 MSCs/kg dose, next six patients receive a single dose of 2 × 106 MSCs/kg, IV |
The incidence of pre-specifed treatment-related adverse events of interest (TRAEIs) |
NCT04348461 |
2 |
Not yet recruiting |
Spain |
Allogeneic adipose MSC |
100 |
Two doses of 1.5 × 106/kg, IV |
Efficacy of the administration of allogeneic mesenchymal stem cells derived from adipose tissue, Safety of the administration of allogeneic mesenchymal stem cells derived from adipose tissue |
NCT04362189 |
2 |
Not yet recruiting |
United States |
Allogeneic adipose MSC |
100 |
Four doses of 1.0 × 108 cells at days 0, 3, 7, and 10, IV |
D-dimer, Interleukin-6, C Reactive protein, Oxygenation, PCR test SARS-CoV-2 |
NCT04397796 |
1 |
Not yet recruiting |
United States |
Allogeneic BM-MSC |
45 |
N/A |
Incidence of AEs, Mortality, Death, Number of ventilator-free days |
NCT04371393 |
3 |
Recruiting |
United States |
Allogeneic BM-MSC |
300 (Placebo:150) |
Two doses of 2 × 106 MSC/kg (doses 4 days apart ± 1 day), IV + standard of care |
Number of all-cause mortality |
NCT04341610 |
1-2 |
Withdrawn |
N/A |
Allogeneic adipose MSC |
N/A |
N/A |
Changes in clinical critical treatment index |
NCT04400032 |
1 |
Not yet recruiting |
Canada |
BM-MSC |
9 |
Intervention group 1: three doses 25 × 106 at day 0, 1, 3 IV Intervention group 2: three doses 50 × 106 at day 0, 1, 3 IV Intervention group 3: three doses 90 × 106 at day 0, 1, 3, IV |
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
NCT04398303 |
1-2 |
Not yet recruiting |
United States |
Allogeneic WJ-MSC |
70 |
Intervention group 1: 1.0 × 106//kg cells in 100 ml CM+ Conventional treatment Intervention group 2: 100 ml CM+ conventional treatment |
Mortality at day 30 |
NCT04389450 |
2 |
Recruiting |
N/A |
Allogeneic ex vivo expanded placental mesenchymal-like adherent stromal cells |
140 |
N/A |
Number of ventilator free days |
NCT04345601 |
1 |
Not yet recruiting |
United States |
Allogeneic BM-MSC |
30 |
Single dose of 1 × 108 cells, IV |
Incidence of unexpected adverse events, Improved oxygen saturations ≥ 93% |
NCT04361942 |
2 |
Recruiting |
Spain |
Allogeneic MSC |
24 |
Single dose of 1 × 106 cells/kg, IV |
Proportion of patients who have achieved withdrawal of invasive mechanical ventilation, Rate of mortality |
NCT04445220 |
1-2 |
Not yet recruiting |
United States |
Allogeneic MSC |
24 |
Low dose cohort: SBI-101 device containing 250 million MSCs; high dose cohort: SBI-101 device containing 750 million MSCs, extracorporeal |
Safety and tolerability as measured by incidence of IP-related serious adverse events |
NCT04397471 |
N/A |
Not yet recruiting |
United Kingdom |
Allogeneic BM-MSC |
10 |
N/A |
Determine feasibility of recruiting healthy volunteers in a clinically useful timeframe, Manufacture a cell-based product suitable for clinical use |
NCT04428801 |
2 |
Not yet recruiting |
United States |
Autologous adipose MSC |
200 |
200 million every 3 days (3 doses), IV |
The overall proportion of subjects who develop any AEs/SAEs related and non-related with the AdMSC infusions as compared to the control group, COVID-19 incidence rates in both the study and control groups |
NCT04366271 |
2 |
Withdrawn |
Spain |
Allogeneic UC-MSC |
106 |
Single IV infusion MSCs (dose unspecified) + standard of care |
Mortality due to long involvement due to SARS-CoV-2 virus infection at 28 days of treatment. Percentage of patients death due to lung involvement due to SARS-CoV-2 virus infection at 28 days of treatment |
NCT04352803 |
1 |
Not yet recruiting |
N/A |
Autologous adipose MSC |
20 |
5 × 105/kg, IV |
Incidence of unexpected adverse events, Frequency of progression to mechanical ventilation, Changes in length of mechanical ventilation, Changes in length of weaning of mechanical ventilation, Changes in length of hospital stay, Changes in mortality rate |
NCT03042143 |
1-2 |
Recruiting |
United Kingdom |
Allogeneic WJ-MSC |
75 |
Single dose of 4 × 108 cells, IV |
Oxygenation index (OI), Incidence of Serious Adverse Events (SAEs) |
NCT04367077 |
2-3 |
Recruiting |
United States |
BM-MSC |
400 |
Dose unspecified, IV |
Ventilator-Free Days, Safety and Tolerability as measured by the incidence of treatment-emergent adverse events as assessed by CTCAE v5.0. |
NCT04535856 |
1 |
N/A |
Indonesia |
Allogeneic MSC |
9 |
N/A |
Incidence of Treatment-Emergent Adverse Event (TEAE) in Treatment Group |
ChiCTR2000029990 |
2 |
Recruiting |
China |
MSC |
120 (Placebo:60) |
1 × 106 per kg of weight, IV |
Improved respiratory system function (blood oxygen saturation) recovery time |
ChiCTR2000029569 |
N/A |
Not recruiting |
China |
UC-MSC |
30 (Placebo:15) |
N/A |
N/A |
ChiCTR2000030138 |
2 |
Not recruiting |
China |
UC-MSC |
60 (Placebo:30) |
Dose unspecified, IV |
N/A |
ChiCTR2000031494 |
1 |
Recruiting |
China |
UC-MSC |
36 (Placebo:18) |
Dose unspecified, IV |
N/A |
ChiCTR2000031430 |
2 |
Recruiting |
China |
UC-MSC |
200 (Placebo:100) |
4 × 107 cells/application on days 0, 3, and 6 for a total of 3 times, IV |
N/A |
Table 1 shows clinical trials using MSCs for the treatment of ARDS due to COVID-19. The data were obtained from clinicaltrials.gov and chictr.org.cn, and these studies can be reviewed on the site with their identifier numbers. In the table, the sources of MSCs used for treatment, the phase of the study, the number of people enrolled in the study, the current status of the study and the countries where the studies were conducted can be seen.
Abbreviations: CT: Computerized Tomography; MSC: Mesenchymal Stem Cell; N/A: Not Available; RT-PCR: Real-Time Polymerase Chain Reaction; CB-MSC: Cord Blood Mesenchymal Stem Cell; UC-MSC: Umbilical Cord Mesenchymal Stem Cell; WJ-MSC: Wharton’s Jelly Mesenchymal Stem Cell; BM-MSC: Bone Marrow Mesenchymal Stem Cell