| Objective:This clinical study aims to use the number of serious adverse events（SAE）as the primary outcome measure to evaluate the safety and efficacy of human umbilical cord-derived mesenchymal stem cells（hUC-MSCs）in children with moderate to severe bronchopulmonary dysplasia（BPD）.Methods:Sixteen participants who met inclusion and exclusion criteria and whose parents had signed the informed consent document were enrolled to hUC-MSCs treatment group,sixteen patients with moderate to severe BPD who had the similar disease condition to hUC-MSCs treatment group were enrolled to the control group.Participants in hUC-MSCs treatment group were treated with low-dose hUC-MSCs（1×106 cells/kg,n=8）and high-dose hUC-MSCs（5×106 cells/kg,n=8）according to the enrollment order.Number of adverse events,changes in vital signs and laboratory tests were recorded before and after hUC-MSCs treatment to assess the safety of hUC-MSCs.Changes in lung injury score（LIS）,Silverman Anderson score and partial pressure of oxygen（PaO2）before and after hUC-MSCs treatment,time of supplemental oxygen therapy and hospital stay after hUC-MSCs treatment,times of respiratory tract infection and readmission,quantitative score of chest CT and lung function test were used to evaluate the efficacy of hUC-MSCs.Results:None of the 16 participants in hUC-MSCs treatment group had SAE associated with infusion after hUC-MSCs treatment,only one had a transient elevation of blood pressure and one had a fever（up to 38.5℃）,and vital signs of the 14 participants were stable.Blood routine test,liver and kidney function test,myocardial markers detection and immune function test were not fluctuated obviously（P>0.05）.To date,two participants died,three had completed a 96-week follow-up,and eleven are under follow-up.The three participants who had completed follow-up had no tumorigenic or teratogenic events.The Silverman Anderson score of hUC-MSCs group was lower than the control group（P<0.05）,LIS had no significant improvement compared with the control group（P>0.05）.PaO2in hUC-MSCs group showed an increasing trend at 24h after treatment,but had no significant difference（P>0.05）,and PaO2 decreased to the baseline level 7 days after treatment.As for time of supplemental oxygen therapy and hospital stay,there were no significant difference between the hUC-MSCs group and the control group（P>0.05）.After discharge,the deoxygenation rate of the surviving participants in the hUC-MSCs group was higher than that in the control group at 1 month and 3 months after treatment.There were no significant difference between the two groups in the number of upper respiratory tract infections and readmission due to respiratory infections.The CT quantitation score of hUC-MSCs group was not significantly improved compared with the control group（P>0.05）,while VPEF%VE and tidal volume of pulmonary function test were significantly improved compared with those before treatment（P<0.05）.Conclusion:The single transplantation of hUC-MSCs through intravenous administration up to 5×106 cells/kg in children with moderate to severe BPD is safe and feasible and there is a certain effect which provided the safety and efficacy evidence for later clinical studies. |
