Table 4 Clinical therapy of MSCs on CARDS
MSCs resource | Clinical phase | Study group | Case | Dose | Delivery method | Delivery time | Outcome measures | Effect | Trial registration | Ref |
|---|---|---|---|---|---|---|---|---|---|---|
UC-MSCs | Phase IIb | Mild-severe CARDS | 21 | 106 cells/kg at three infusions | Intravenously | Diagnosed for < 96 h | Primary outcomes: respiratory improvement assessed; secondary outcomes: clinical improvements. | D0-to-D7 PaO2/FiO2 changes did not differ significantly. | IRCT20200621047859N4 | |
PL-MSCs | Phase I | Moderate-severe CARDS | 10 | 106 cells/kg at a single infusion | Intravenously | More than 96 h have passed since the diagnosis of CARDS | Main outcomes: the safety of transplantation. | The mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different. | NCT04333368 | |
BM-MSCs | Phase I/II | Severe CARDS | 8 | 3.15 ×106cells/kg at three infusions | Intravenously | Within 2 days of ICU admission | Safety outcomes: tolerability and adverse events related to MSCs; efficacy outcomes. | Higher survival in the MSC cohort; no significant difference in the need for mechanical ventilation nor the number of invasive ventilation-free days, high flow nasal oxygenation-free days, oxygen support-free days and ICU-free days. | NCT04445454 | |
UC‐MSCs | Phase I/IIa | Mild-severe CARDS | 12 | 100 ± 20 × 106cells at two infusions | Intravenously | At day 0 and day 3 | Primary outcomes: safety, adverse events; Secondary outcomes: clinical improvements and laboratory testing and mechanistic analyses. | Inflammatory cytokines were significantly decreased, and survival and time to recovery were improved in the MSC cohort; | NCT04355728 | |
BM-MSCs | A case series | Moderate-severe CARDS | 11 | 2 × 106 cells/kg at two infusions | Intravenously | Given 48–120 h apart | Primary outcomes: ICU mortality; Secondary outcomes: clinical improvements. | Improved liberation from mechanical ventilation and discharge from the ICU and/or hospital with significantly declined CRP levels； | / | |
UC-MSCs/ PL-MSCs | A case series | Mild-severe CARDS | 11 | 200 × 106cells at three infusions | Intravenously | Every other day | Main outcomes: the safety and potential adverse events; | Reduced dyspnea and increased SpO2 were observed with decreased inflammatory biomarkers including TNF-α, IL-8, IL-6, CRP, IFN-γ; Four patients with multi-organ failure or sepsis died in 5-19 days after the first MSC infusion. | / | |
UC-MSCs | A case series | Moderate-severe CARDS | 13 | 106 cells/kg at three infusions | Intravenously | On treatment days 0, 3, and 6 | Safety and clinical improvements | Decreased inflammatory markers, more rapid recovery of blood lymphocytes, and reduced SP-D | / | |
UC-MSCs | A case series | Severe CARDS | 5 | 106 cells/kg at a single infusion | Intravenously | / | Adverse events and clinical improvements | Improved respiratory function, anti-inflammatory capacity | / | |
UC-MSCs | Phase I | Severe CARDS | 20 | 106 cells/kg at a single infusion | Intravenously | On day 8 (ranged from day 2‐30) of treatment in the ICU | Primary outcome: survival rate and/or length of ventilator usage; clinical and laboratory improvement, with serious adverse events | Increased the survival rate; anti-inflammatory by decreasing IL-6 | NCT04457609 | |
PL-MSCs | A case series | Moderate to severe CARDS | 5 | 200 ± 20 × 105cells at two infusions | Intravenously | on Days 0 and 4. | Safety and clinical efficacy. | Suppressed hyper-inflammatory states | / | |
BM-MSCs | Phase II/III | Moderate to severe CARDS | 112 | 2 × 106 cells/kg at two infusions | Intravenously | The second infusion 4 days after the first infusion | Primary outcomes: reduction in all-cause mortality within 30 days; secondary outcomes: days alive off mechanical ventilation within 60 days. | MSCs did not improve 30-day survival or 60-day VFD in patients with moderate and/or severe CARDS. | NCT04371393 | |
UC-MSCs | Phase I | Non-severe CARD | 10 | 1 × 106 cells/kg at three infusions | Intravenously | Every other day (days 1, 3 and 5) | Primary outcome: the safety of three doses; secondary outcomes: changes in specific biomarkers of inflammatory dysregulation. | MSC improved respiratory function and cytokine storm reduction in CARDS and increased the number of injections can increase patients’ recovery. | IRCT20160809029275N1 | |
Decidua-MSCs | A case series | Mild-severe CARDS | 10 | 1 × 106 cells/kg at 1-2 infusions | Intravenously | After 3 days in patients needing more than one dose | Safety and efficacy by survival, oxygenation and effects on levels of cytokines | Improved oxygenation, decreased inflammatory cytokine levels and cleared pulmonary infiltrates in CARDS. | / |
