Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer's disease.
Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer's disease.
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DOI：
10.1186/s13195-021-00791-x
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发表时间：
2021-03-06
期刊：
影响因子：
--
通讯作者：
Baulch JE
中科院分区：
文献类型：
--
作者：
Apodaca LA;Baddour AAD;Garcia C Jr;Alikhani L;Giedzinski E;Ru N;Agrawal A;Acharya MM;Baulch JE
缓解阿尔茨海默病(AD)神经病理的再生疗法显示出非常有限的成功。近年来，来源于多能和多能干细胞的细胞外小泡(EVS)在治疗痴呆和许多神经退行性疾病方面显示出巨大的前景。使用5xFAD加速的AD转基因小鼠模型，我们现在展示了人类神经干细胞(HNSC)来源的EV对AD大脑的神经认知和神经病理特征的再生潜力。两个月或六个月龄的5xFAD小鼠分别接受一次或两次静脉内(眶后静脉，RO)注射hNSC来源的EV。在注射4-6 周后，使用hNSC来源的EVS进行RO治疗，恢复了恐惧，消除了记忆，巩固了记忆，减少了焦虑相关行为。EV治疗还显著减少了两个年龄组的致密核心淀粉样β斑块堆积和小胶质细胞激活。这些结果与AD小鼠体内循环促炎细胞因子水平的部分恢复有关。重要的是，EV治疗保护了AD大脑中与认知改善平行的突触丢失。对EV货物的miRNA分析显示，针对神经炎症和突触功能的候选药物前景看好。总而言之，这些数据证明了全身应用干细胞衍生的EV对行为和分子AD神经病理的补救作用的神经保护作用。网上版载有补充材料，可在10.1186/s13195-021-00791-x查阅。
Regenerative therapies to mitigate Alzheimer’s disease (AD) neuropathology have shown very limited success. In the recent era, extracellular vesicles (EVs) derived from multipotent and pluripotent stem cells have shown considerable promise for the treatment of dementia and many neurodegenerative conditions. Using the 5xFAD accelerated transgenic mouse model of AD, we now show the regenerative potential of human neural stem cell (hNSC)-derived EVs on the neurocognitive and neuropathologic hallmarks in the AD brain. Two- or 6-month-old 5xFAD mice received single or two intra-venous (retro-orbital vein, RO) injections of hNSC-derived EVs, respectively. RO treatment using hNSC-derived EVs restored fear extinction memory consolidation and reduced anxiety-related behaviors 4–6 weeks post-injection. EV treatment also significantly reduced dense core amyloid-beta plaque accumulation and microglial activation in both age groups. These results correlated with partial restoration of homeostatic levels of circulating pro-inflammatory cytokines in the AD mice. Importantly, EV treatment protected against synaptic loss in the AD brain that paralleled improved cognition. MiRNA analysis of the EV cargo revealed promising candidates targeting neuroinflammation and synaptic function. Collectively, these data demonstrate the neuroprotective effects of systemic administration of stem cell-derived EVs for remediation of behavioral and molecular AD neuropathologies. The online version contains supplementary material available at 10.1186/s13195-021-00791-x.
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影响因子：
16.2
作者：
Edbauer, Dieter;Neilson, Joel R.;Foster, Kelly A.;Wang, Chi-Fong;Seeburg, Daniel P.;Batterton, Matthew N.;Tada, Tomoko;Dolan, Bridget M.;Sharp, Phillip A.;Sheng, Morgan
通讯作者：
Sheng, Morgan
DOI：
10.3233/jad-142766
发表时间：
2015
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Khalsa DS
通讯作者：
Khalsa DS
DOI：
10.1037/0097-7403.29.4.323
发表时间：
2003-10-01
期刊：
JOURNAL OF EXPERIMENTAL PSYCHOLOGY-ANIMAL BEHAVIOR PROCESSES
影响因子：
--
作者：
Cain, CK;Blouin, AM;Barad, M
通讯作者：
Barad, M
影响因子：
6.2
作者：
Baulch, Janet E.;Acharya, Munjal M.;Agrawal, Anshu
通讯作者：
Agrawal, Anshu
影响因子：
2.7
作者：
Bonardi, Charlotte;de Pulford, Felicity;Pardon, Marie-Christine
通讯作者：
Pardon, Marie-Christine