Mesenchymal stem cells

Umbilical cord mesenchymal stem cell (UC-MSC) therapy was safe in COVID-19 ARDS patients and resulted in decreased inflammatory cytokine levels at day 6, improvement of patient survival, more frequent serious adverse events-free survival, and shorter time to recovery. Sample size: 12 + 12 placebo. Dosage: Two IV doses of 100 ± 20 × 106 UCâ€ÂMSCs 3 days apart (in vehicle solution containing human serum albumin and heparin). Outcomes: Safety (primary outcome).

Exosomes (ExoFlo™) derived from allogeneic bone marrow mesenchymal stem cells. Patients received a single 15 mL intravenous dose of ExoFlo and were evaluated for both safety and efficacy from days 1 to 14 post-treatment. All safety endpoints were met with no adverse events observed within 72 h of ExoFlo administration. 

The stem cell therapy was safe and well tolerated. In the small cohort of patients, those treated with mesenchymal stem cells had better overall outcome compared to the ones who were not. 4 of the 5 patients in the treatment group survived, but only 8 out of the 18 patients in the control group did, despite being in a slightly better overall condition at the baseline. Sample size: 5 + 18 control. Dosage: 1-3 infusions of 10^6 cells per kg of body weight.

exploration of placenta-derived MSCs (P-MSCs) to therapeutically perquisite in ameliorating immune-mediated progressive worsening in COVID-19 infected patients

UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was −13.31%, 95% CI −29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: −15.45%; 95% CI −30.82%, −0.39%; P = 0.043). The 6-minute walk test showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057).

Human umbilical cord mesenchymal stem cell therapy was well-tolerated in moderate to severe COVID-19 patients. No statistically significant difference in clinical parameters was observed between the treatment group and the control. Sample size: 9 + 9 control. Dosage: 3 transfusions of 3×10^7 cells, 3 days apart. Primary outcome: Safety.

The pulmonary function and symptoms of the patient with COVID-19 pneumonia was significantly improved in 2 days after human umbilical cord Wharton’s jelly-derived MSCs transplantation, and recovered and discharged in 7 days after treatment.

After allogenic hUCMSCs were given 3 times (5×10⁷ cells each time) with a 3-day interval, together with thymosin α1 and antibiotics daily injection, most of the laboratory indexes and CT images showed remission of the inflammation symptom. 

The administration of allogeneic human umbilical cord MSC in comorbid COVID-19 patients with severe ARDS was generally safe and the adverse reactions were manageable. Three of the 5 treated patients improved so that they could be extubated. Two patients died. MSC therapy was associated with improvement in respiratory functions. Sample size: 5. Dosage: Single infusion of 10^6 cells/kg.

MSCs (1 × 10⁶ cells per kilogram of weight) could cure or significantly improve the functional outcomes of all seven patients without observed adverse effects. 

The treatment of PBMC from COVID-19 patients with MSCs isolated from dental pulp altered the activated T-lymphocytes’ cytokine secretion in a way suggesting its use to alleviate the inflammatory state associated with COVID-19. 

Treatment with CD362-enriched umbilical cord-derived MSCs was considered safe (observed serious adverse effects were not related to the treatment). Mortality among the treatment cohort (moderate to severe ARDS patients) was 44%. Sample size: 3 + 3 + 3. Dosage: 1x10^8 or 2x10^8 or 4x10^8 cells ("3 + 3" dose escalation scheme). Main outcome: incidence of serious adverse events.

Improvement in clinical parameters without adverse effects was observed. Sample size: 7 + 3 placebo. Dosage: 10^6 cells per kg. 

The authors propose to use UC-MSCs treatment followed by tocilizumab treatment to suppres COVID-19-linked ARDS. The hypothesis is based on the observation that co-cultivation of UC-MSCs with PBMCs suppresses their inflammatory response upon phytohemagglutinin treatment. 

Intratracheal administration (in a murine model of ARDS induced by LPS) of bone marrow MSC-derived small extracellular vesicles led to a reduction in markers of ARDS and inflammation and increase in oxygenation levels.

In two COVID-19 cases, application of menstrual blood-derived MSCs was followed by improvement in clinical status as assessed via inflammatory, immune, respiratory or radiological findings. Sample size: 2. Dosage: 10^6 cells per kg. 

In the treatment group, no progression to critical disease was observed. The time to clinical improvement was shorter and the treated patients displayed signs of recovery (improvement in physiological functions, biochemical markers or radiological findings). The treatment was considered safe. Sample size: 12 + 29 control. Dosage: 2x10^6 cells per kg. 

Allogenic MSCs derived from Wharton’s jelly were administered to a patient with ARDS and multiorgan failure due to COVID-19. The first three doses were intravenous, the fourth was partially IV and partially intrathecal. Clinical improvement was observed. Sample size: 1. Dosage: 4 doses of 10^6 cells pre kg. 

Combined with tocilizumab. The treatment was safe. Continual clinical improvement leading to recovery was observed. Sample size: 1. Dosage: 0.5x10^6 cells per kg every other day (3 doses total). 

The treatment was well tolerated. The treated patient’s clinical condition improved so that he could be discharged from hospital. Sample size: 1. Dosage: 3 doses of 10^6 cells per kg. 

Clinical improvement and recovery were observed in a critically ill COVID-19 patient. No severe adverse reactions were noted. Sample size: 1. Dosage: 2 administrations of (0.7x10^6 cells per kg IV + 0.3x10^6 cells per kg intratracheal) 5 days apart. 

The treatment was considered safe. In most of the treated patients, clinical improvement was observed (based on oxygenation, pulmonary CT imaging or IgM levels). No significant change was observed in several biochemical markers, however. Sample size: 12 + 13 control. Dosage: 10^6 cells per kg. 

The treatment was safe. Reduction of inflammation and improvement in oxygenation were observed. Sample size: 31. Dosage: 10^6 cells per kg. 

An ICU patient post Caesarean section received MSCs infusion and clinical improvement was observed. A patient who received immune serum instead of MSCs succumbed to the infection. Sample size: 1 + 1 control. 

Patients in the treatment group had statistically significantly shortened length of hospital stay and the time for symptoms remission, compared to the ones receiving placebo. Improvement in chest radiological findings was observed in more severe cases, too. MSCs derived from umbilical cord have been shown to reduce biomarkers of inflammation, inhibit neutrophil extracellular traps and promote the maintenance of SARS-CoV-2-specific antibodies. This activity could be facilitated via regulation of immune cells (B cell subsets and stimulation of CD28 expression in T cells) and hematopoietic stem/progenitor-like cells. A murine model showed a potential to reduce venous thrombosis, as well. Sample size: 29 + 29 placebo. Dosage: 10^6 cells per kg. Main outcome: The median time of hospital stay.

Extracellular vesicles (EV) derived from placental MSCs were not cytotoxic and suppressed SARS-CoV-2 infection in vitro. Contained micro RNAs miR-let-7b-5b, miR-21-5p, miR-92a-3p, miR-24-3p, and miR-181a-5p are possibly contributing to the anti-inflammatory activity of MSC-derived EVs. 

Based on in vitro studies on patient peripheral blood mononuclear cells, free or microencapsulated MSCs derived from Wharton’s jelly were shown to modulate several immune pathways misregulated due to COVID-19. Sample size: 18 cell donors. 

Using models of SARS-CoV-2-induced acute lung injury, the authors show that extracellular vesicles derived from BM-MSCs could reduce inflammation, increase active ACE2 surface protein and alleviate respiratory dysfunction. 

An analysis of plasma samples from COVID-19 ARDS patients treated with UC-MSCs suggests that soluble TNF receptor 2 mediates the observed therapeutical effect of the stem cells on TNFα and TNFβ levels. This could explain the decrease of inflammation in the treated patients. Sample size: 12 + 12 control. 

Clinical improvement, including increase in total lymphocyte counts, was observed in a critically ill COVID-19 patient. Sample size: 1. Dosage: 10^6 cells per kg. 

The treatment likely led to clinical improvement and reduction in mortality in critically ill COVID-19 patients. Sample size: 10  (critical illness) + 10 control (critical illness) + 10 control (moderate illness). Dosage: 3 doses of 3x10^6 cells per kg, 3 days apart. 

Most of the patients did not experience side effects, but there were cases of liver dysfunction, heart failure and allergic rash. There were no significant changes in laboratory findings regarding inflammation. Majority of the severe COVID-19 patents experienced clinical improvement and recovery following the treatment, however. Sample size: 25. Dosage: 1-3 doses of 10^6 cells per kg, 5 days apart. 

The treatment was well-tolerated. Rapid improvement in oxygenation and lung injury were observed. Mortality was slightly lower compared to other studies with confirmed ARDS patients (although higher compared to similar studies considering unconfirmed ARDS). Sample size: 22. Dosage: 10^6 cells per kg. 

The treatment was safe. It improved oxygenation and displayed significant efficacy if applied prior to intubation (at early stages of severe infection). Sample size: 99 (intubated) + 111 (unintubated). Dosage: 1-2x10^6 cells per kg. 

Combined with convalescent plasma, a possible synergy in inducing clinical and laboratory improvement was observed. Sample size: 1. Dosage: 10^6 cells per kg every 3 days (3 doses total). 

The therapy was considered safe. 4 critically ill patients who had developed sepsis or multi-organ failure died after a single dose, in such patients, the therapy might not be suitable. In other patients, clinical improvement was observed – rapid alleviation of respiratory distress. Reduction in biomarkers of inflammation was noted in some patients. Sample size: 6 UC-MSCs + 5 P-MSCs. Dosage: A total of 6x10^8 cells in three doses two days apart. Main outcome: Safety.

Patients were examined 3 months after the treatment. No significant adverse reactions were observed. Accelerated lung recovery indicators and higher health-related quality of life were observed among the treated patients compared to the control group. Sample size: 8 + 20 control. Dosage: 2x10^6 cells per kg. 

The treatment was not associated with adverse effects. It was generally associated with a decrease in inflammatory markers and an increase in lymphocyte counts. Clinical improvement was observed in majority of the cases. Sample size: 13. Dosage: Mostly 2 doses of median 0.98x10^6 cells per kg; median 3 days apart. 

Statistically significantly lower mortality was observed in patients treated with menstrual blood-derived MSCs compared to a control group. The incidence of adverse reactions was generally similar in these two groups. In the treated patients, improvement in respiratory functions and chest imaging results was observed, as well. Sample size: 26 + 18 control. Dosage: 9x10^7 cells total in 3 doses. 

The therapy using Wharton’s jelly-derived MSCs was generally well tolerated and amelioration of inflammation was observed in the treated paients. Sample size: 5. Dosage: 3 doses of 1.5x10^8 cells 3 days apart. 

Following the treatment, improvement in the counts of T cells and reduction in inflammatory cytokines and myeloid cells was observed. Immunosuppressive functions of low-density gradient neutrophils and circulating monocytes were activated. From the clinical perspective, respiratory, renal, inflammatory, and pro-thrombotic indexes were improved. Sample size: 1. Dosage: 1.1x10^6 cells per kg. 

The treatment was safe. Improvement in lymphocyte counts, radiological findings and oxygenation was observed. Mortality within the cohort was lower than that which is generally observed in a similar setting. Sample size: 16. Dosage: 4 doses of 10^8 cells one day apart. Main outcome: The oxygenation index on day 14.

The treatment might have slowed down the progression of the disease. The critically ill patient died after lung transplant rejection in the end, however. Sample size: 1. Dosage: 5 doses 1.5x10^6 cells per kg 48 hours apart. 

The overall survival in the treatment group was significantly higher compared to the control group. The treatment correlated with decrease in IL-6 levels. It was generally safe. The length of ICU stay was insignificantly longer in the treatment group. Differences in blood biomarkers were statistically insignificant between the groups. Sample size: 20 + 20 placebo. Dosage: 10^6 cells per kg. Main outcome: Survival rate and/or length of mechanical ventilation.

Patients treated with MSCs displayed lower volume of lung lesions. There was not significant difference in tumour markers, adverse reactions, or neutralization antibody levels between the groups. Sample size: 65 (56 for 1-year follow-up) + 35 (30 for 1-year follow-up) placebo. Dosage: 4x10^7 cells on days 1, 4, and 7. Main outcome: Proportion of whole-lung lesion volumes assessed by high-resolution CT.

The treatment was safe and an early administration of the MSCs showed promise in the prevention of cytokine storm onset. The overall survival was favourable. Sample size: 14. Dosage: Two doses of 5x10^7 cells, in average 5 days apart or a single dose of 10^8 cells. 

After the treatment during an advanced stage of COVID-19, clinical improvement was observed (including pulmonary function, radiological findings and systemic inflammation markers). Sample size: 1. Dosage: 2 doses of 5x10^7 cells. 

The treatment likely led to clinical improvement and reduction of inflammation in a critically ill COVID-19 patient. Sample size: 1. Dosage: 6.4x10^7 cells on days 28 and 31, 6.5x10^7 cells on days 59, 63 and 66, and 3 doses of 6.5x10^7 cells one week apart during rehabilitation. 

Mesenchymal stem cell (MSC)-derived exosomes were observed to inhibit neutrophil extracellular trap release and interleukin 17 production by neutrophils in vitro. This led the authors to hypothesize a potential of MSC exosomes to mitigate immune dysregulation in acute respiratory failure observed in COVID-19 patients. 

In patients with mild COVID-19 pneumonia, inhalation of nebulized mesenchymal stem cell-derived exosomes did not lead to adverse reactions. Absorption of pulmonary lesions and relatively short length of hospital stay were observed. Sample size: 7. Dosage: Nebulization twice a day using 5 ml of solution (7x10^7 to 7.66x10^8 particles pre ml). Main outcome: Safety-related (secondary infection, allergic reactions, and life-threatening adverse events).

The formulation of nebulized exosomes derived from adipose tissue mesenchymal stromal cells was well tolerated. Clinical improvement within 7 days, as assessed by CT imaging, was observed in all subjects. Sample size: 7. Dosage: 2x10^8 vesicles daily for 5 days. Main outcome: Prespecified inhalation-associated events and serious adverse effects.

Three days after transfusion of human placental derived mesenchymal stromal cells, the clinical status of critically ill infant diagnosed with COVID-19 started to improve (and was ultimately discharged from hospital). Sample size: 1. Dosage: 2 infusions of 7x10^6 cells each, two days apart. 

The treatment using human placenta-derived mesenchymal stromal cells was safe in critically ill patients with COVID-19-related ARDS. There was no statistically significant difference between the treatment and the control groups. The authors conclude that the obtained results warrant further studies. Sample size: 10 + 10 control. Dosage: A single infusion of 10^6 cells/kg. Main outcome: Safety.

Clinical improvement was observed in moderately ill COVID-19 patients treated with a mixture of umbilical cord- and placenta-derived mesenchymal stromal cells. There was no control group. Sample size: 10. Dosage: Two infusions of 10^8 cells, 3 days apart. Main outcome: Safety.

The treatment using bone marrow-derived MSCs was safe. The outcomes and overall survival were generally favourable (not statistically significantly different from control). The day 7 D-dimer levels were significantly lower in the treated severe COVID-19 patients. Sample size: 8 + 8 retrospective matched control. Dosage: 3 infusions of 1.5-3x10^6 cells/kg 3 (± 1) days apart. 

The treatment using human umbilical cord-derived MSCs was safe in the long term. The outcomes and overall survival were generally favourable and there was statistically significant improvement in KL-6 levels, MDA levels, and fatigue relief in the treated patients compared to the control. Sample size: 8 + 17 control. Dosage: 2x10^6 cells/kg. Main outcome: Adverse effects.

The treatment using umbilical cord mesenchymal stem cells resulted in no serious adverse effects. There was a significant improvement in observed respiratory functions and markers of inflammation. No changes were observed using CT imaging. Sample size: 10 + 10 placebo. Dosage: Three infusions of 10^6 cells/kg two days apart. Main outcome: Safety.

In a rat model of ARDS (induced by LPS), placental mesenchymal stem cell treatment reduced inflammatory cytokine levels and contributed to restoration of lung tissue structure and function. The findings could be of use in the field of COVID-19 therapy research. 

The treatment of pneumonia patients using exosomes derived from umbilical cord MSCs was safe and led to favourable outcomes (e.g., absorption of pulmonary lesions, reduced length of hospital stay). Sample size: 7. Dosage: 7x10^7 to 7.66x10^8 particles per ml diluted in 5 ml of physiological solution. Main outcome: Safety.

Administration of umbilical cord mesenchymal stem cells in severe to critical COVID-19 pneumonia patients was followed by a significant decrease in hs-CRP and monocyte distribution width, a decrease in various other markers of inflammation and by a significant improvement in pulmonary functions. Sample size: 4 + 4 control. Dosage: One or two doses of 10^8 cells. 

An elderly patient with severe COVID-19 displayed rapid improvement in markers of inflammation after the administration of the first dose. This improvement was only transient, however. On day 9, two days after the administration of the second dose, the patient succumbed to a bacterial infection. The authors suggest, that observation of early indicators of cytokine storm will be appropriate for timing of MSC therapy, which might be provided in multiple doses. Sample size: 1. Dosage: Two doses of 3x10^8 cells distributed in 15 intramuscular injections each. 

The treatment generally led to clinical improvement in several measured parameters in critically ill COVID-19 patients. Sample size: 8. Dosage: One or two doses of 3x10^8 (“PLAX-PAD”) cells distributed in 15 intramuscular injections (each). 

The treatment led to improvement in the levels of markers of inflammation, improvement in respiratory function, and alleviation of lung injury in critically ill COVID-19 patients with moderate to severe ARDS. Sample size: 5 + 19 control. Dosage: 2 IV infusions of 2×10^7 placenta-derived MSCs (“MatriPlax”), 4 days apart.