Feasibility Of Adipose Stem Cells Derived Bioactive Secretome For Infants With Moderate/Severe Hypoxic-Ischemic Encephalopathy

Background and Objective:Hypoxic-Ischemic Encephalopathy is brain injury caused by factors induced hypoxia and ischemia during perinatal period.It is the main cause of death in new born.Those survivals always have long-term disability in function of motor,sensor and recognition.With the development of modern medicine,more infants suffered hypoxic ischemic insults survived,therefore,disability rate increased greatly.So far,the only legal therapy for HIE in developed country is hyperthermia.But the effect is still limited.Based on animal experiment,we want to assess feasibility and safety of intrathecal administration of Adipose Stem Cells derived Bioactive Secretome to neonates with moderate/severe HIE.Methods:98 neonates diagnosed with moderate/sever HIE were enrolled during September 2013 to June 2016 in 9 hospitals'NICU.44 patients were assigned to have intrathecal injections of ASC-BS,while 54 patients were assigned to controlled group.All received conventional treatment,patients in experimental group accepted 3 dosage intrathecal injection of ASC-BS in the first 72 hours after birth.All patients,baseline characteristics,pre-and post-infusion vital signs,neural manifestations and adverse events caused by intervention were recorded.NBNA at 28 day and mortality at discharge were recorded as hospital outcomes.At 18 months after birth,Survivals' Bayley Scales(China City Version),Peabody Development Measure Scales,rate of patient without neural disability,rate of cerebral palsy and rate of global developmental delay were taken as long-term outcomes.SPSS 19.0 was used for statistical analysis.Results:1.Short-term outcomes:Mortality had no significant difference between two groups(p>0.05).Compared with controlled group,infants treated with ASC-BS had higher NBNA scores at 28 days after birth(p<0,05).2.Long-term outcomes assessed at 18 month after birth:i.Bayley Scales(China City Version):more patients in ASC-BS group got scores>85 in mental scales(p=0.03);more patients in ASC-BS group got scores?85 in mental scales(p=0.04).ii.Peabody Development motor scales:There was no significant difference between two groups in gross motor quotient(p>0.05);Rate of patients who had scores>85 in fine motor quotient was higher in ASC-BS group(p=0.01);Rate of patients who had scores>85 in total motor quotient was higher in ASC-BS group(p-0.02).iii.84.21%ASC-BS recipients and 60.47%in controlled group survived without any neural developmental disorder(p =0.02).iv.Rate of cerebral palsy had no significant difference between two groups(p>0.05).v.2.63%ASC-BS recipients and 18.6%in controlled group were diagnosed with global developmental delay(p=0.05).3.Side effect:Low fever in 3 cases,5 patients showed irritation disappeared in 2 hours after injection and disappeared in 24 hours.Conclusion:The intrathecal injection of Adipose Stem Cells derived Bioactive Secretome for patients with HIE in the first 72 hours are feasible and safe.This kind of intervention revealed neuroprotection and did not induced significant clinical problems associated with secretions.A randomized phase II study is warranted which may consider improve the scheme of administration to achieve better neural and systematic protection.