Efficacy Of Stem Cell Therapy In Animal Models Of Intracerebral Hemorrhage

Purposes:Several studies have found that stem cell therapy can reduce brain tissue damage and improve neurological function in animal models of cerebral hemorrhage.We conducted an updated systematic review and meta-analysis of preclinical data published in recent years on stem cell therapy for cerebral hemorrhage,and systematically analyzed the efficacy of stem cell therapy in animal models of cerebral hemorrhage.Methods:The preclinical studies up to November 18,2021 on stem cell therapy for cerebral hemorrhage were searched in mainstream databases such as PUBMED,EMBASE and Web of Science.We extracted the basic characteristics,neural behavioral scale scores,pathological changes of brain tissue and other items.The random effect model was applied to meta-analysis with the use of Comprehensive Meta-analysis(CMA)software.Results:1.62 studies were included in the meta-analysis.According to the CAMARADES score,the median methodological quality score was 5.30(total score was 10),of which 48 studies(77.42%)were high-quality studies(≥5 points),and 14 studies(22.58%)were low-quality studies(<5 points).2.Stem cell therapy can alleviate the neurological impairment and pathological damage of brain tissue after cerebral hemorrhage.The standardized mean difference(SMD)of the modified neurological severity score(mNSS)after cerebral hemorrhage was-2.27,and the SMD of the rotarod test was-2.14,the SMD of modified limb placement test(MLPT)was-2.06,the SMD of cylinder test was-1.33,the SMD of comer turn test was-1.95,the SMD of brain tissue loss was-1.42,and the SMD of brain water content was-1.86.3.There were significant differences in the improvement of mNSS score in different quality research subgroups(p=0.013).The improvement of mNSS score is much better in high quality research subgroup(SMD=-2.57)than low quality research subgroup(SMD=-1.59).4.There were significant differences in the improvement of mNSS score between different administration methods(p=0.002),among which intraperitoneal administration was the best(SMD=-4.63).5.Stem cell therapy reduced brain tissue loss after intracerebral hemorrhage,which was related to the methods of establishment of animal models.The reduction of brain tissue loss was better in autologous blood-induced intracerebral hemorrhage subgroup(SMD=-1.84)than in collagenase-induced intracerebral hemorrhage subgroup(SMD=-0.94,p=0.035).6.There were significant differences in the reduction of brain tissue loss among different intervention time point after intracerebral hemorrhage(p=0.035).Stem cell therapy within 8 hours after intracerebral hemorrhage had the best effect in reducing brain tissue loss(SMD=-2.72,95%CI:(-3.81,-1.62),p<0.001).Conclusions:(1)Stem cell therapy reduced the neurological impairment and pathological damage of brain tissue after cerebral hemorrhage,and contributed to he recovery of cerebral hemorrhage.(2)The improvement of mNSS score was more significant in high-quality study subgroup and intraperitoneal administration subgroup.(3)The alleviation of brain tissue loss was more significant in the autologous blood-induced intracerebral hemorrhage subgroup and in the subgroup that started stem cell therapy within 8 hours after intracerebral hemorrhage.This study contains 14 figures,4tables and 89 references.