人脐带间充质干细胞在正常C57BL/6J小鼠和自身免疫性脑脊髓炎小鼠的体内生物分布对比研究  

Comparative study on the biodistribution of human umbilical cord mesenchymal stem cells in normal C57BL/6J and experimental autoimmune encephalomyelitis mice

作　　者：郝晓芳 朱灏 秦超 姜华[1] 李倩倩[1] 黄瑛[1] 李波[1,2] HAO Xiaofang;ZHU Hao;QIN Chao;JIANG Hua;LI Qianqian;HUANG Ying;LI Bo(National Center for Safety Evaluation of Drugs,China National Institute for Food and Drug Control,Beijing 100176,China;China National Institute for Food and Drug Control,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China;Sinoneural Cell Engineering Group Co.,Ltd.,Shanghai 200240,China)

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心/药物非临床安全评价研究北京市重点实验室,北京100176 [2]中国医学科学院北京协和医学院中国食品药品检定研究院,北京100730 [3]华夏源细胞工程集团有限公司,上海200240

出　　处：《中国医药生物技术》2025年第2期146-153,共8页Chinese Medicinal Biotechnology

基　　金：国家重点研发计划(2021YFA1101602);中国食品药品检定研究院关键技术研究基金(GJJS-2022-6-1)。

摘　　要：目的研究人脐带间充质干细胞在正常C57BL/6J小鼠和多发性硬化症模型实验性自身免疫性脑脊髓炎(EAE)小鼠体内的生物分布。方法采用Di R近红外荧光染料标记技术标记人脐带间充质干细胞,回输到正常C57BL/6J小鼠和EAE小鼠体内,在给予干细胞后2 h、3 h、1 d、3 d、5 d、7 d、10 d、14 d进行活体成像示踪干细胞,14 d后剖检小鼠,对心脏、肝脏、脾脏、肺脏、脑、脊柱(含脊髓)进行组织成像。结果DiR标记人脐带间充质干细胞静脉回输给予小鼠后,荧光值在体内呈现先升高后降低的趋势,在正常C57BL/6J小鼠中2d到达峰值,在疾病模型小鼠中1d达到峰值;在正常C57BL/6J小鼠中10 d检测不到荧光信号,在疾病模型小鼠中10 d仍能检测到荧光信号,14 d荧光信号消失。组织成像研究显示干细胞单次尾静脉给予正常和疾病模型小鼠后,细胞在体内至少存续14d,集中分布于肺脏、肝脏、脾脏等部位。结论人脐带间充质干细胞在多发性硬化症模型EAE小鼠体内比在正常C57BL/6J小鼠中存续时间更长,且MSC在EAE疾病小鼠中具有更明显的脾脏归巢作用。Objective To study the biodistribution of human umbilical cord mesenchymal stem cells in normal C57BL/6J mice and experimental autoimmune encephalomyelitis mice,a model of multiple sclerosis.Methods Human umbilical cord mesenchymal stem cells were labelled using the DiR near-infrared fluorescent dye labeling technique and infused back into normal C57BL/6J mice and experimental autoimmune encephalomyelitis mice.Live imaging was performed to trace the stem cells at 2 h,3 h,1 d,3 d,5 d,7 d,10 d,and 14 d after administration of the stem cells.Mice were sacrificed after 14 d and tissue imaging of heart,liver,spleen,lung,brain,and spine(including spinal cord)was performed.Results After DiR-labelled human umbilical cord mesenchymal stem cells were given to mice by intravenous,the mesenchymal stem cells showed a tendency of increasing and then decreasing in vivo,reaching a peak at day 2 in normal C57BL/6J mice and day 1 in disease model mice.Fluorescent signals were undetectable at day 10 in normal C57BL/6J mice,and still detectable at day 10 in disease model mice,and undetectable at day 14.In the normal animals,the cells were not detected for day 10,and were still detectable for day 14 in model mice.The results from tissue imaging studies showed that after a single tail vein administration of stem cells to normal C57BL/6J and disease model mice,the cells survived for at least 14 days in vivo,and concentrated in the lung,liver and spleen.Conclusions Human umbilical cord mesenchymal stem cells survive for at least 14 days in normal C57BL/6J mice and experimental autoimmune encephalomyelitis mice after intravenous administration,mainly homing to the lungs,liver and spleen,etc.Human umbilical cord mesenchymal stem cells may survive longer in experimental autoimmune encephalomyelitis disease mice,a model of multiple sclerosis,than in normal C57BL/6J animals.And human umbilical cord mesenchymal stem cells have a more pronounced splenic homing effect experimental autoimmune encephalomyelitis disease mice.

关 键 词：脐带间充质干细胞 C57BL/6J小鼠 实验性自身免疫性脑脊髓炎 活体成像 生物分布 

分 类 号：R744.51[医药卫生—神经病学与精神病学]