Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome.
Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome.
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DOI：
10.3390/ijms24043477
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发表时间：
2023-02-09
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
唐氏综合症（DS），或称21三体，表现为多种解剖和细胞异常，导致智力缺陷和阿尔茨海默病（AD）的早期发病，目前尚无有效的治疗方法来缓解与该疾病相关的病理。细胞外囊泡（EVs）的治疗潜力最近在各种神经系统疾病中出现。我们之前已经在恒河猴皮质损伤模型中证明了间充质基质细胞衍生的ev （msc - ev）在细胞和功能恢复方面的治疗效果。在目前的研究中，我们评估了msc - ev在由患者来源的诱导多能干细胞（iPSCs）产生的DS的皮质球体（CS）模型中的治疗效果。与整倍体对照相比，三体CS表现出更小的尺寸，神经发生缺陷和ad相关的病理特征，如细胞死亡和淀粉样蛋白（Aβ）和过度磷酸化tau （p-tau）的沉积增加。与未处理的三体CS相比，ev处理的三体CS显示出保留的大小，神经元产生的部分恢复，a β和p-tau水平显著降低，细胞死亡程度降低。综上所述，这些结果表明ev在缓解人类CS中DS和ad相关的细胞表型和病理沉积方面的功效。
Down syndrome (DS), or trisomy 21, is manifested in a variety of anatomical and cellular abnormalities resulting in intellectual deficits and early onset of Alzheimer’s disease (AD) with no effective treatments available to alleviate the pathologies associated with the disorder. The therapeutic potential of extracellular vesicles (EVs) has emerged recently in relation to various neurological conditions. We have previously demonstrated the therapeutic efficacy of mesenchymal stromal cell-derived EVs (MSC-EVs) in cellular and functional recovery in a rhesus monkey model of cortical injury. In the current study, we evaluated the therapeutic effect of MSC-EVs in a cortical spheroid (CS) model of DS generated from patient-derived induced pluripotent stem cells (iPSCs). Compared to euploid controls, trisomic CS display smaller size, deficient neurogenesis, and AD-related pathological features, such as enhanced cell death and depositions of amyloid beta (Aβ) and hyperphosphorylated tau (p-tau). EV-treated trisomic CS demonstrated preserved size, partial rescue in the production of neurons, significantly decreased levels of Aβ and p-tau, and a reduction in the extent of cell death as compared to the untreated trisomic CS. Together, these results show the efficacy of EVs in mitigating DS and AD-related cellular phenotypes and pathological depositions in human CS.
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