人骨髓间充质干细胞脑内注射给予食蟹猴的长期毒性研究  

Long-term toxicity of human BMSC injected in cerebrum of cynomolgus monkey

作　　者：李岩[1] 高虹[1] 李秦[1] 朱华[1] 韩钦[2] 安沂华[3] 赵春华[2] 王任直[4] 秦川[1] 

机构地区：[1]中国医学科学院实验动物研究所,北京100050 [2]中国医学科学院基础医学研究所 [3]北京市神经外科研究所 [4]北京协和医院神经外科

出　　处：《毒理学杂志》2010年第2期89-93,共5页Journal of Toxicology

基　　金：国家"863"高科技研究计划项目(No.2006AA02A115)

摘　　要：目的研究人骨髓间充质干细胞(BMSC)脑内注射给予食蟹猴的长期毒性,为临床试验提供依据。方法24只食蟹猴随机分为对照组(生理盐水)、低剂量组(3×105个细胞/kg)和高剂量组(2.5×106个细胞/kg),每只动物脑内基底节外囊区域定向注射人BMSC2次,间隔3周。注射后观察动物的一般毒性反应,并进行体重、体温、神经功能、心电图、血液学和血液生化学、体液免疫(IgG、IgM)、细胞免疫(CD3、CD4、CD8)、尿液、脑脊液(一般性状、细胞计数、葡萄糖、蛋白质和氯化物含量)及组织病理学等指标测定。结果病理结果显示食蟹猴脑内基底节外囊区域注射人BMSC后,注射部位大脑局部出现组织坏死及炎症反应,对照组、低剂量组和高剂量组的损伤程度和范围呈递增趋势,随着时间推移,各组脑组织病变基本修复,残存少量瘢痕组织。其他各项检测指标均未见有生物学意义的显著改变。结论在本试验条件下,2.5×106/kg的剂量范围内,人BMSC食蟹猴脑内基底节外囊区域注射仅对注射局部大脑组织产生一定的病理损伤,损伤可随着时间推移逐渐修复。Objective To evaluate long-term toxicity of human BMSC injected in cerebrum of cynomolgus monkey,and to provide evidence for clinical application. Methods 24 cynomolgus monkeys were assigned to 3 groups randomly： the control （NS）,low dosage（3 × 105 /kg）and high dosage（2. 5 × 106 /kg）. BMSC or NS was injeceted into capsula externa region of basal ganglia of each cynomolgus monkey for 2 times,dosing interval for three weeks. The indicators of general toxic reaction,body weight,body temperature, neuron-function, electrocardiogram,hematology and the blood biochemistry, routine urinalysis, humoral and cell immunity and cerebrospinal fluid were monitored,histopathologic examination was also performed. Results The histopathologic results showed that human BMSC induced pathologic damage of the injection site including local tissue necrosis and inflammation. The damage of low dose and high dose group were greater than that of control group,yet over time, the damage could be repaired gradually. No significant BMSC associated toxic reactions were noted from other indicators. Conclusion Under the dosage of 2. 5 × 106 /kg,human BMSC injected in capsula externa region of basal ganglia induced pathologic damage of the injection site of cerebrum,and the damage could be repaired gradually.

关 键 词：骨髓间充质干细胞 长期毒性 脑内注射 食蟹猴 

分 类 号：R114[医药卫生—卫生毒理学]