Human neural stem cell transplantation improves cognition in a murine model of Alzheimer's disease.
Human neural stem cell transplantation improves cognition in a murine model of Alzheimer's disease.
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DOI：
10.1038/s41598-018-33017-6
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发表时间：
2018-10-03
影响因子：
4.6
通讯作者：
Feldman EL
中科院分区：
文献类型：
--
作者：
McGinley LM;Kashlan ON;Bruno ES;Chen KS;Hayes JM;Kashlan SR;Raykin J;Johe K;Murphy GG;Feldman EL
干细胞移植为治疗神经退行性疾病提供了一种潜在的变革性方法。细胞疗法的安全性是在多个临床试验中建立的，包括我们自己的肌萎缩性侧索硬化症。要在阿尔茨海默病中开展类似的试验，必须确定有效的细胞系。在这里，我们完成了APP/PS1阿尔茨海默病小鼠模型的临床前概念验证研究。针对穹窿穹窿的人类神经干细胞移植在移植后4周和16周显著改善了海马依赖记忆任务的认知。虽然突触相关蛋白和胆碱能神经元的水平不受影响，但干细胞移植小鼠的淀粉样斑块负荷显著减少，并与激活的小胶质细胞募集增加有关。在体外，这些相同的神经干细胞诱导小胶质细胞活化和淀粉样蛋白吞噬，表明免疫调节能力。尽管长期移植导致APP/PS1小鼠的功能和病理显著改善，但在研究终点未通过免疫组织化学或PCR鉴定出干细胞。这些数据表明整合到原生组织中，或者短暂植入可能足以达到治疗效果，减少持续免疫抑制的需要。总之，我们的研究结果支持人类神经干细胞作为一种安全有效的阿尔茨海默病治疗方法的进一步临床前开发。
Stem cell transplantation offers a potentially transformative approach to treating neurodegenerative disorders. The safety of cellular therapies is established in multiple clinical trials, including our own in amyotrophic lateral sclerosis. To initiate similar trials in Alzheimer’s disease, efficacious cell lines must be identified. Here, we completed a preclinical proof-of-concept study in the APP/PS1 murine model of Alzheimer’s disease. Human neural stem cell transplantation targeted to the fimbria fornix significantly improved cognition in two hippocampal-dependent memory tasks at 4 and 16 weeks post-transplantation. While levels of synapse-related proteins and cholinergic neurons were unaffected, amyloid plaque load was significantly reduced in stem cell transplanted mice and associated with increased recruitment of activated microglia. In vitro, these same neural stem cells induced microglial activation and amyloid phagocytosis, suggesting an immunomodulatory capacity. Although long-term transplantation resulted in significant functional and pathological improvements in APP/PS1 mice, stem cells were not identified by immunohistochemistry or PCR at the study endpoint. These data suggest integration into native tissue or the idea that transient engraftment may be adequate for therapeutic efficacy, reducing the need for continued immunosuppression. Overall, our results support further preclinical development of human neural stem cells as a safe and effective therapy for Alzheimer’s disease.
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影响因子：
11.2
作者：
Chen KS;Sakowski SA;Feldman EL
通讯作者：
Feldman EL
影响因子：
7.5
作者：
Duncan T;Valenzuela M
通讯作者：
Valenzuela M
DOI：
10.1016/j.trci.2015.06.007
发表时间：
2015-09
期刊：
Alzheimer's & dementia (New York, N. Y.)
影响因子：
--
作者：
Kim HJ;Seo SW;Chang JW;Lee JI;Kim CH;Chin J;Choi SJ;Kwon H;Yun HJ;Lee JM;Kim ST;Choe YS;Lee KH;Na DL
通讯作者：
Na DL
在阿尔茨海默氏病鼠模型的海马中，VEGF过表达的VEGF过表达骨髓间充质干细胞的治疗作用。
影响因子：
4.8
作者：
Garcia KO;Ornellas FL;Martin PK;Patti CL;Mello LE;Frussa-Filho R;Han SW;Longo BM
通讯作者：
Longo BM
通过脊柱移植治疗肌萎缩侧索硬化症的人类神经干细胞替代疗法。
影响因子：
3.7
作者：
Hefferan MP;Galik J;Kakinohana O;Sekerkova G;Santucci C;Marsala S;Navarro R;Hruska-Plochan M;Johe K;Feldman E;Cleveland DW;Marsala M
通讯作者：
Marsala M