Understanding Immune-Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform.
Understanding Immune-Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform.
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DOI：
10.1002/advs.202200475
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发表时间：
2022-09
期刊：
影响因子：
--
通讯作者：
Guo F
中科院分区：
文献类型：
--
作者：
Ao Z;Song S;Tian C;Cai H;Li X;Miao Y;Wu Z;Krzesniak J;Ning B;Gu M;Lee LP;Guo F
免疫系统的老化驱动全身老化和年龄相关疾病的发病机制。然而，由于目前神经免疫相互作用的体外模型有限，在理解免疫驱动的衰老，特别是大脑衰老方面仍然存在重大的知识差距。在这里，作者报告了人类大脑类器官微生理分析平台（MAP）的开发，以发现免疫驱动的大脑衰老的动态过程。类器官MAP由3D打印创建，限制类器官生长并促进细胞和营养灌注，促进类器官成熟及其对前脑身份的承诺。将动态摇摆流纳入平台，允许灌注来自年轻（20至30岁）和老年（>60岁）供体的原代单核细胞，并培养人皮质类器官以模拟神经免疫相互作用。作者发现，衰老的单核细胞增加浸润并促进衰老相关标志物的表达（例如，p16的更高表达），表明老化的单核细胞可能会导致脑老化。作者认为，类器官MAP可能为衰老、神经免疫疾病、自身免疫性疾病和癌症的基础研究和转化应用提供有前途的解决方案。报道了人脑类器官微生理分析平台的开发，以模拟免疫-脑相互作用，并且从老年供体中发现的单核细胞可能驱动脑老化。
The aging of the immune system drives systemic aging and the pathogenesis of age‐related diseases. However, a significant knowledge gap remains in understanding immune‐driven aging, especially in brain aging, due to the limited current in vitro models of neuroimmune interaction. Here, the authors report the development of a human brain organoid microphysiological analysis platform (MAP) to discover the dynamic process of immune‐driven brain aging. The organoid MAP is created by 3D printing that confines organoid growth and facilitates cell and nutrition perfusion, promoting organoid maturation and their committment to forebrain identity. Dynamic rocking flow is incorporated into the platform that allows to perfuse primary monocytes from young (20 to 30‐year‐old) and aged (>60‐year‐old) donors and culture human cortical organoids to model neuroimmune interaction. The authors find that the aged monocytes increase infiltration and promote the expression of aging‐related markers (e.g., higher expression of p16) within the human cortical organoids, indicating that aged monocytes may drive brain aging. The authors believe that the organoid MAP may provide promising solutions for basic research and translational applications in aging, neural immunological diseases, autoimmune disorders, and cancer. The development of a human brain organoid microphysiological analysis platform to model immune–brain interaction is reported and the monocytes found from aged donors may drive brain aging.
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