两种状态脐血间充质干细胞移植对脑梗死大鼠神经功能恢复的对比研究  

Transplantation of umbilical cord blood mesenchymal stem cells at two states: comparison of neurological function recovery in cerebral infarction rats

作　　者：韩小改[1] 李建斌[1] 单泓[1] 别立莉[1] 王娇杰 刘英[1] 戚正[1] Han Xiao-gai;Li Jian-bin;Shan Hong;Bie Li-li;Wang Jiao-jie;Liu Ying;Qi Zheng(Department of Blood Composition,Henan Red Cross Blood Center,Zhengzhou 450012,Henan Province,China)

机构地区：[1]河南省红十字血液中心成分室,河南省郑州市450012

出　　处：《中国组织工程研究》2018年第9期1395-1401,共7页Chinese Journal of Tissue Engineering Research

基　　金：河南省科技攻关项目(201204120)~~

摘　　要：背景:脐血间充质干细胞对缺血缺氧引起的神经细胞损伤具有修复作用,而原代分离的和经过诱导分化的细胞,何种状态的治疗效果好未有定论。目的:比较原代分离的和经过培养诱导分化的2种状态脐血间充质干细胞对大鼠脑梗死模型治疗效果。方法:(1)取足月分娩的胎儿脐血,经四联袋梯度密度离心法分离脐血间充质干细胞;(2)通过含有碱性成纤维生长因子的培养基诱导分化脐血间充质干细胞;(3)将60只大鼠随机等分为4组:假手术组、模型组、原代细胞治疗组及诱导分化细胞治疗组,后3组建立脑梗死模型。原代细胞治疗组及诱导分化细胞治疗组分别在造模后7 d通过尾静脉注射原代分离的和经过培养诱导分化的2种状态脐血间充质干细胞。结果与结论:移植原代分离的和经过培养诱导分化的2种状态脐血间充质干细胞的脑梗死模型大鼠平衡、行走、空间定位和学习记忆能力得到明显改善,且其中与原代分离的脐血间充质干细胞治疗的大鼠相比,经诱导分化的脐血间充质干细胞治疗的大鼠脑梗死体积接近,脑组织病理损伤改善更为明显,脑组织中CD34、Ki-67阳性细胞数量较高,神经胶质纤维酸性蛋白阳性细胞数量较低,脑组织中炎症因子白细胞介素1β和肿瘤坏死因子β表达减少,而白细胞介素6表达水平接近。说明经过培养诱导分化的脐血间充质干细胞对脑梗死模型大鼠神经功能的治疗效果更佳。BACKGROUND:Human umbilical cord blood mesenchymal stem cells(hUC-MSCs)can repair the injury of nerve cells caused by ischemia and hypoxia,but which state of cells has a better therapeutic efficacy,primary isolation or induced differentiation is not yet known.OBJECTIVE:To compare the therapeutic effects of hUC-MSCs primary cultured and differentiated in a rat model of cerebral infarction.METHODS:After full-term delivery,fetal umbilical cord blood samples were obtained using quadruple bags by means of density gradient centrifugation.hUC-MSCS were induced in the medium containing basic fibroblast growth factor.Sixty rats were equivalently randomized into four groups:sham,model,primary culture and induced differentiation groups.Animal models of cerebral infarction were made in the rats in the latter three groups.Model rats in the primary culture and induced differentiation groups were subjected to tail vein transplantation of hUC-MSCs that were primary cultured or induced to differentiate in vitro at 7 days after modeling.RESULTS AND CONCLUSION:A marked improvement in balance,walking,spatial orientation,and learning and memory abilities was found in the rats after transplantation of hUC-MSCs that were primary cultured or induced to differentiate.Moreover,compared with the primary culture group,a significant improvement was found in the induced differentiation group,including improved pathological injury of the brain,higher expression of CD34 and Ki-67,lower expression of glial fibrillary acidic protein,lower expression of interleukin 1βand tumor necrosis factorβ.Compared with the primary culture group,similar infarction size and expression of interleukin-6 were also found in the induced differentiation group.These findings indicate that hUC-MSCs with induced differentiation exhibit better therapeutic outcomes in the recovery of neurological function of cerebral infarction rats.

关 键 词：脐血干细胞移植 梗塞 大脑中动脉 组织工程 

分 类 号：R394.2[医药卫生—医学遗传学]