Mononuclear cell therapy of neonatal hypoxic-ischemic encephalopathy in preclinical versus clinical studies:A systematic analysis of therapeutic efficacy and study design  

作　　者：Alexander M.Scrutton Francesca Ollis Johannes Boltze 

机构地区：[1]School of Life Sciences,University of Warwick,Coventry,UK [2]Neurobiology Division,MRC Laboratory of Molecular Biology,University of Cambridge,Cambridge,UK

出　　处：《Neuroprotection》2023年第2期143-159,共17页神经保护（英文）

基　　金：Academy of Medical Sciences(Newton Advanced Fellowship),Grant/Award Number:NAF\R11\1010。

摘　　要：Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns globally.Therapeutic hypothermia(TH)can reduce mortality and,to a limited extent,disability after HIE.Nevertheless,there is a need for new and effective treatment strategies.Cell-based treatments using mononuclear cells(MNCs),which can be sourced from umbilical cord blood,are currently being investigated.Despite promising preclinical results,there is currently no strong indicator for the clinical efficacy of the approach.This analysis aimed to provide potential explanations for this discrepancy.Methods:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Preclinical and clinical studies were retrieved from PubMed,Web of Science,Scopus,and clinicaltrials.gov using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were included.We analyzed overall MNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical trials.Results:There was evidence for MNC therapeutic efficacy in preclinical models of HIE.The methodological quality of preclinical studies was not optimal,and statistical design quality was particularly poor.However,methodological quality was above the standard in other fields.There were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher MNC doses being applied in preclinical studies.Conclusions:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical studies.It is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in HIE.Additional preclinical and clinical research is required to optimize the application of MNC for experime

关 键 词：cell therapy hypoxic-ischemic encephalopathy mononuclear cells translational research treatment efficacy 

分 类 号：R722.1[医药卫生—儿科]