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SOD1G93A ALS小鼠脊髓内注射人间充质基质细胞

Intraspinal injection of human mesenchymal stromal cells in SOD1G93A ALS mice
课程网址: http://videolectures.net/encals2017_bursch_stromal_cells/  
主讲教师: Franziska Bursch
开课单位: 汉诺威医学院
开课时间: 2017-07-21
课程语种: 英语
中文简介:
导言:细胞治疗正在被讨论为治疗神经退行性疾病如肌萎缩侧索硬化症(ALS)的新的治疗选择。ALS的细胞治疗目前侧重于为运动神经元创造保护性环境,而不是细胞替代。间充质基质细胞(MSC)已被证明分泌不同的生长因子并具有抗凋亡特性。因此,它们似乎适合创建一个神经保护微环境。由于MSC可以方便、安全地从人骨髓中分离出来,因此MSC有望用于进一步的临床前和临床评估。方法:采用符合GMP的方法分离人骨髓间充质干细胞(hMSCs)。在第一项研究中,SOD1G93A转基因ALS小鼠(B6.SJL Tg(SOD1-G93A)1Gur/J)在症状出现前(第40天)接受椎管内注射hMSCs(双侧每侧注射1x105个细胞,体积为1µl)或生理盐水作为载体对照。在第二项研究中,在症状出现之前和之后(第40天和第90天),对小鼠进行椎管内注射治疗。一组动物在这两天接受生理盐水,一组动物在第40天接受hMSCs,第90天接受生理盐水,第三组动物在这两天接受hMSCs。通过生存分析、体重测量和根据行为评分每日评估一般情况,评估hMSCs可能的保护作用。电机性能通过rotarod和足迹分析进行监控。结果/结论:我们的体内研究结果显示,第40天注射hMSC对体重减轻和步长(仅雄性动物)有显著影响,并且有增加存活率和改善一般状况和运动能力的趋势。双重注射研究的初步结果显示重复椎管内注射hMSC对运动性能(运行时分析)和体重减轻有显著影响。正在进行的研究包括脊髓组织的组织学分析,以及比较脊髓内注射和鞘内注射的进一步动物研究。
课程简介: Introduction: Cellular therapy is being discussed as novel therapeutic option for the treatment of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Cell therapy for ALS currently focuses on the generation of a protective environment for motor neurons instead of cell replacement. Mesenchymal stromal cells (MSC) have already been shown to secrete different growth factors and have anti-apoptotic properties. They therefore appear suitable to create a neuroprotective microenvironment. As they can easily and safely be isolated from human bone marrow, MSC are promising candidates for further preclinical and clinical evaluation. Methods: Human bone marrow derived mesenchymal stromal cells (hMSCs) are isolated by a previously established GMP-conform protocol. In the first study, SOD1G93A transgenic ALS mice (B6.SJL-Tg(SOD1-G93A)1Gur/J) receive intraspinal injections of either hMSCs (bilateral injections of 1x105 cells per side in a volume of 1µl as described), or saline as vehicle control before symptom onset (day 40). In a second study, mice are treated by intraspinal injections before and after symptom onset (day 40 and day 90). One group of animals receives saline on both days, one receives hMSCs at day 40 and saline at day 90 and the third group hMSCs at both days. Possible protective effects of hMSCs are evaluated by survival analysis, measurement of body weight and daily assessment of general condition according to a behavioral score. Motor performance is monitored via rotarod and footprint analysis. Results/Conclusions: The results of our in vivo studies reveal a significant effect of hMSC injections at day 40 on weight loss and on step length (in male animals only) as well as a trend towards increased survival and improvement in general condition and motor performance. Preliminary results of the double injection study show significant effects of repeated intraspinal hMSC injections on motor performance (runtime analysis) and weight loss. Ongoing studies contain histological analyses of spinal cord tissue and further animal studies comparing intraspinal injection and intrathecal injections.
关 键 词: 细胞治疗; 肌萎缩侧索硬化症; 间充质基质细胞
课程来源: 视频讲座网
数据采集: 2021-12-22:zkj
最后编审: 2021-12-22:zkj
阅读次数: 74