人骨髓间充质干细胞脑内移植对食蟹猴脑出血的治疗作用  

Intracerebral transplantation of human bone marrow mesenchymal stem cells promotes the functional recovery in Macaca fascicularis with intracerebral hemorrhage

作　　者：朱华[1] 冯铭[2] 卢珊[3] 李秦 刘颖[1] 陈云新[1] 代小伟[1] 李昊 孙井江[1] 安沂华[5] 赵春华[3] 王任直[2] 秦川[1] 

机构地区：[1]中国医学科学院&北京协和医学院比较医学中心&国家中医药管理局人类疾病动物模型三级实验室 [2]中国医学科学院北京协和医院,北京1000730 [3]中国医学科学院基础医学研究所,北京1000055 [4]中国医学科学院医学实验动物研究所Motac合作实验室,北京100021 [5]北京神经外科研究所,北京100039

出　　处：《中国实验动物学报》2011年第5期361-365,I0001,I0002,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：863课题(编号:2006AA02A115)

摘　　要：目的评价人骨髓间充质干细胞脑内移植对食蟹猴脑出血模型的治疗作用。方法符合普通级标准的成年食蟹猴12只,用自体股动脉抗凝血脑内注射方法建模后1周,用脑立体定位法在血肿周围植入人骨髓间充质干细胞,细胞数分别为高剂量5×106、低剂量1×106、对照组等体积生理盐水。利用MRI、PET、神经功能缺损评分和组织病理学对干细胞移植效果进行评价。结果神经功能评分显示干细胞移植1周后动物神经功能明显改善。PET结果显示干细胞移植后2周高剂量组血肿周围皮层、基底节核团的SUV%值与对照组间存在显著性差异(P=0.02)。移植后3周高、低剂量组血肿周围皮层、基底节核团的SUV%值与对照组间差异存在显著性(P值分别为0.03和0.04)。MRI显示剂量组血肿吸收速度大于对照组。病理检查可见剂量组坏死灶面积小于对照组,出血灶周围有大量新生血管生成,剂量组与对照组间差异存在显著性(P<0.01)。结论在损伤脑组织周围移植hBMSC可促进食蟹猴损伤神经组织的恢复,为hBMSC治疗脑出血的临床应用提供了重要实验依据。Objective To investigate the therapeutic effect of human bone marrow-derived mesenchymal stem cell（hBMSC） transplantation on experimentally induced intracerebral hemorrhage in Macaca fascicularis,and to examine the effects of hBMSC transplantation on the recovery of neurological function.Methods In 12 Macaca fascicularis,autologous femoral arterial blood was injected into the brain parenchyma to develop an intracerebral hemorrhage（ICH） model.The animals were randomly divided into high-dose,low-dose,and control groups.After one week,250 μl of hBMSC in amount of 5×106,1×106 cells,or saline were injected at the edge of the hematoma,respectively.High field MR scanning and positron-emission tomography（PET） scans were performed weekly before and after the hBMSC transplantation.Neurological functions were evaluated weekly,and the brains were taken for pathological examination at 4 weeks after hBMSC transplantation.Results After hBMSC transplantation,neural function scores were improved significantly in the high-and low-dose groups compared with that of the control group.Two weeks after transplantation,the surrounding area of the hematoma exhibited a circular elevated standardized uptake value（SUV）,and the SUV% of the putamen in the high-dose group was significantly higher than that of the control group（P=0.02）.At 3 weeks after transplantation,the SUV percentages of the putamen and thalamus in the high-dose group were significantly higher than that of the the control group（P=0.03 and 0.04,respectively）.At 4 weeks after transplantation,pathological examination showed a large amount of neovasculature around the ICH after hBMSC transplantation in the transplantation groups compared with that in the control group（P0.01）.Conclusions Intracerebral transplantation of human bone marrow mesenchymal stem cells can improve the functional recovery of damaged cerebral tissue in Macaca fascicularis.It provides important experimental evidence indicating the use of hBMSC to restore neurological deficits in

关 键 词：间充质干细胞 脑出血 移植 食蟹猴 

分 类 号：Q95-33[生物学—动物学]