利用生物相容性聚合物大规模生产人类皮质类器官

IF 26.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Genta Narazaki, Yuki Miura, Sergey D. Pavlov, Mayuri Vijay Thete, Julien G. Roth, Merve Avar, Sungchul Shin, Ji-il Kim, Zuzana Hudacova, Sarah C. Heilshorn, Sergiu P. Pașca
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引用次数: 0

摘要

从人类多能干细胞中产生神经类器官在疾病建模和药物筛选方面具有很大的前景,但目前的方法由于不希望的类器官融合而难以扩展。在这里,我们通过筛选生物相容性聚合物来开发可扩展的大脑皮质类器官平台,这些聚合物可以防止悬浮培养的类器官融合。我们确定了一种具有成本效益的多糖,可以增加培养基的粘度,显著提高皮质类器官的产量,同时保留区域模式、神经元形态和功能活性等关键特征。我们进一步证明,该平台可以直接筛选298种fda批准的药物和致畸物,使用超过2400种皮质类器官来治疗生长缺陷,发现破坏类器官生长发育的药物。我们期望这种方法为模拟人类皮层发育提供一个强大的、可扩展的系统,并促进神经精神疾病相关表型的有效化合物筛选。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Scalable production of human cortical organoids using a biocompatible polymer

The generation of neural organoids from human pluripotent stem cells holds great promise in modelling disease and screening drugs, but current approaches are difficult to scale due to undesired organoid fusion. Here we develop a scalable cerebral cortical organoid platform by screening biocompatible polymers that prevent the fusion of organoids cultured in suspension. We identify a cost-effective polysaccharide that increases the viscosity of the culture medium, significantly enhancing the yield of cortical organoids while preserving key features such as regional patterning, neuronal morphology and functional activity. We further demonstrate that this platform enables straightforward screening of 298 FDA-approved drugs and teratogens for growth defects using over 2,400 cortical organoids, uncovering agents that disrupt organoid growth and development. We anticipate this approach to provide a robust and scalable system for modelling human cortical development, and facilitate efficient compound screening for neuropsychiatric disorders-associated phenotypes.

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来源期刊
Nature Biomedical Engineering
Nature Biomedical Engineering Medicine-Medicine (miscellaneous)
CiteScore
45.30
自引率
1.10%
发文量
138
期刊介绍: Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.
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