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通过人脑类器官模型深入了解病毒诱导的神经发育障碍

Advancing insights into virus-induced neurodevelopmental disorders through human brain organoid modelling.

作者信息

Crawford Gabriella, Soper Olivia, Kang Eunchai, Berg Daniel A

机构信息

Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.

出版信息

Expert Rev Mol Med. 2024 Nov 26;27:e1. doi: 10.1017/erm.2024.35.

DOI:10.1017/erm.2024.35
PMID:39587735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11707831/
Abstract

Human neurodevelopment is a complex process vulnerable to disruptions, particularly during the prenatal period. Maternal viral infections represent a significant environmental factor contributing to a spectrum of congenital defects with profound and enduring impacts on affected offspring. The advent of induced pluripotent stem cell (iPSC)-derived three-dimensional (3D) human brain organoids has revolutionised our ability to model prenatal viral infections and associated neurodevelopmental disorders. Notably, human brain organoids provide a distinct advantage over traditional animal models, whose brain structures and developmental processes differ markedly from those of humans. These organoids offer a sophisticated platform for investigating viral pathogenesis, infection mechanisms and potential therapeutic interventions, as demonstrated by their pivotal role during the 2016 Zika virus outbreak. This review critically examines the utilisation of brain organoids in elucidating the mechanisms of TORCH viral infections, their impact on human brain development and contribution to associated neurodevelopmental disorders.

摘要

人类神经发育是一个复杂的过程,容易受到干扰,尤其是在孕期。母体病毒感染是一个重要的环境因素,可导致一系列先天性缺陷,对受影响的后代产生深远而持久的影响。诱导多能干细胞(iPSC)衍生的三维(3D)人脑类器官的出现,彻底改变了我们对产前病毒感染及相关神经发育障碍进行建模的能力。值得注意的是,人脑类器官相对于传统动物模型具有明显优势,传统动物模型的脑结构和发育过程与人类明显不同。这些类器官为研究病毒发病机制、感染机制和潜在治疗干预提供了一个精密的平台,2016年寨卡病毒爆发期间它们所起的关键作用就证明了这一点。这篇综述批判性地审视了脑类器官在阐明TORCH病毒感染机制、其对人类脑发育的影响以及对相关神经发育障碍的作用方面的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57e0/11707831/3dc4b610b243/S1462399424000358_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57e0/11707831/f688e82c7fc0/S1462399424000358_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57e0/11707831/3dc4b610b243/S1462399424000358_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57e0/11707831/f688e82c7fc0/S1462399424000358_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57e0/11707831/3dc4b610b243/S1462399424000358_fig2.jpg

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iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer.iPS 细胞衍生的小胶质细胞通过胆固醇转移促进类器官成熟。
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