Safety And Short Term Efficacy Of Adipose Stem Cells Derived Bioactive Secretome In Treating White Matter Injury Of Premature

Objective White Matter Injury(WMI)is one of the main types of encephalopathy of preterm infants.It can lead to neurological sequelae such as cerebral palsy and cognitive impairment.There is still no effective treatment currently.Stem cell technology shows great potential for neurological rehabilitation.Increasing studies suggest that stem cells produce therapeutic effects through paracrine mechanisms.This study is about a multicenter clinical trial of intrathecal injection of Adipose Stem Cells derived Bioactive Secretome(ASCBS)in the treatment of White Matter Injury(WMI)in preterm infants,in which we clarified the clinical safety and curative effects of ASCBS on the mental and motor neurodevelopment at corrected age of 6 months and explored the feasibility and key directions for further clinical study.Methods A task group formed with a number of hospitals across the country led by PLA Naval General Hospital recruited 63 cases of WMI according to common standards from multiple hospitals into 3 gestational age subgroups,which were Subgroup A(gestational age 240-286),Group B(gestational age 290-326),Group C(gestational age 330-366).The patients were randomly divided into treatment groups and control groups.The treatment group received lumbar puncture followed with ASCBS intrathecal injection once daily for 3 consecutive days.Both groups received the same routine treatment,nursing and follow-up.The clinical changes after ASCBS injection and the main complications of premature infants were recorded and their correlation with ASCBS was evaluated.Follow-up included Neonatal Behavioral Neurological Assessment(NBNA)score at term-equivalent age and Neurodevelopment at corrected age of 6-month.Neurodevelopment was assessed using the Bailey Scales of Infant Development(BSID)and Peabody Developmental Motor Scale(PDMS-2).Safety assessments were performed by post-injection adverse reactions observing of ASCBS and comparison of survival rate and complication rate between the treatment group and the control group.The short-term efficacy evaluation was performed by comparison of the NBNA scores,Mental Develop Index(MDI)and Psychomotor Develop Index(PDI)of the BSID assessment,and quotient of gross,fine,and total motor development of PDMS-2.Results Among the 63 cases recruited,11 were in treatment group A,10 in control group A,10 in treatment group B,10 in control group B,10 in group treatment C and 12 in control group C.One case of treatment group A was lost during follow-up.Other patients were completely followed up.No clinical negative events after ASCBS were recorded in each treatment group.There was no significant difference in survival rate or in complication incidences of preterm birth between treatment group and control group in all subgroups(P>0.05).However,in the statistics about complications,the incidence of pulmonary hemorrhage in the treatment group A was higher than that in the control group A,P=0.063,The gross and total motor development quotients of PDMS-2 in treatment group A at corrected age of 6 months were higher than those in control group A with statistically significant.The details of gross motor development quotients were as follows:98.33±6.282 in treatment group A,90.33±3.777 in control group A,(P=0.040).The details of total motor development quotient were as follows:97.33±4.803 in treatment group A,91.00±4.472 in control group A,(P=0.023).It showed no significant difference between treatment group A and control group A in the NBNA scores at term-equivalent age,fine motor development quotient of PDMS-2 or any results of BSID at corrected age of 6-month(P>0.05).Neither did it in the results of NBNA scores,PDMS-2 or BSID in subgroup B and C(P>0.05).Conclusions The ASCBS treatment of WMI in preterm infants is safe and can promote the motor development of preterm infants with gestational age at 240-286.For the next step,researchers should enlarge the sample size,extend the follow-up duration and pay attention to the respiratory system changes such as pulmonary hemorrhage after ASCBS treatments in preterm infants of small gestational age.