May mesenchymal stem cell transplantation be a solution for COVID-19 induced cytokine storm?

Table 1 Promising mesenchymal stem cells studies

Ref.	MSC type	Sample size	Dose	Outcome
Leng et al[86]	ACE2- MSC	10 patients (7 MSC + 3 Placebo)	Single infusion 106 cells/kg cells IV, 40 min	A decrease of TNF-α and an increase of anti-inflammatory IL-10 were significant (P < 0.05). Other outcome data consisted of one critically ill patient. Three of the 7 patients who taken MSC discharged in the follow-up period
Zhang et al[77]	Human umbilical cord Wharton’s jelly-derived MSCs (hWJCs)	One critically ill patient	Single infusion 106 cells/kg cells IV, 40 min	The patient was discharged 6 d after the administration. They suggested that remarkable amelioration in imaging, laboratory, and clinical test outcomes
Sánchez-Guijo et al[87]	Adipose tissue-derived MSC (AT-MSC)	13 severe ill patients	More than 1 infusion approximately 106 cells/kg cells IV	Two patients died during the follow-up period. They detected a decrease in inflammatory parameters and an increase in total lymphocyte counts 5 d after administration
Sengupta et al[88]	Bone marrow MSCs derived exosomes	24 patients	Single infusion 15 ml ExoFloTM IV	The study's survival rate is 83%, and 71% of the patients were recovered in the study interval. The outcome of the study is a clinical improvement with an average PaO2/FiO2 rate increase of 192% (P < 0.001)
Peng et al[89]	UC-MSCs and CP	1 severe ill patient	Two times infusion plasma volume 400 mL (Total) (1:160 titer SARS-CoV-2 specific IgG); 3 times infusion 106 cells/kg (Total) IV 30-40 min	Lack of response to CP treatment, MSCs were administrated to the patient. After the clinical improvement, the patient was discharged
Liang et al[78]	UC-MSCs	1 critically ill patient	3 times infusion 5 × 107 cell (each time) with thymosin-a1 IV	Clinical and laboratory improvement had been seen; The patient was discharged 17 d after the first MSC infusion
Tang et al[90]	Menstrual blood-derived MSCs	2 patients	3 times infusion 106/kg cells	Imaging and laboratory improvement had been seen
Shu et al[91]	UC-MSCs	41 severe ill patients (12 MSC treatment + 29 Placebo)	Single infusion 2 × 106 cells/kg IV 60 min	In treatment arm progression from severe to critical illness and 28-d mortality rate were 0, while 4 patients deteriorated to critical condition and 3 of them died, 28 d mortality rate was 10.34%. The treatment arm’s clinical and laboratory improvements were significantly faster than the placebo group
Tao et al[92]	Human umbilical cord blood-derived MSCs	1 critically ill patient	5-times infusion 1.5 × 106 cells/kg (each time) IV 60-80 min	After the MSC treatment, related to the clinical condition, the patient had undergone lung transplantation. The patient died 6 d after the transplantation because of the rejection
Feng et al[93]	UC-MSCs	16 severe and critically ill patients	4 times with one-day intervals 1 × 108 cells once 90 min	The primary outcome was oxygenation index on day 14, and it has improved after UC-MSCs transplantation. On day 28, there is no significant difference between severe and critical types’ mortality rates (6.25%)
Guo et al[94]	UC-MSCs	31 severe and critically ill patients	106/kg cells in 100 mL saline 200 mL (median volume) for each patient	They reported a significant increase in lymphocyte count, PaO2/FiO2, and decrease CRP, D-Dimer, IL-6, procalcitonin

UC: Umbilical cord; MSC: Mesenchymal stem cell; AT: Adipose Tissue; CP: Convalescent plasma; IL: Interleukin; PaO₂: Partial pressure of oxygen; FiO₂: Fraction of inspired oxygen; CRP: C reactive protein.