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Engineering stem cell-derived 3D brain organoids in a perfusable organ-on-a-chip system

机译:工程干细胞衍生的3D脑器有机体在灌注的电机上系统中

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摘要

Brain organoids derived from the self-organization of human induced pluripotent stem cells (hiPSCs) represent a new class of in vitro organ system for modeling brain development and diseases. However, engineering brain organoids in a biomimetic environment that is favorable for brain development remains challenging. In this work, we present a new strategy to generate hiPSCs-derived 3D brain organoids using an organ-on-a-chip system in a controlled manner. This system provides a biomimetic brain microenvironment by incorporating three-dimensional (3D) Matrigel, fluid flow and multicellular architectures of tissues that allows for extended 3D culture, in situ neural differentiation, and organization of brain organoids on a single device. The generated brain organoids display well-defined neural differentiation, regionalization and cortical organization under perfused culture conditions, which recapitulate the key features of early human brain development. Moreover, the brain organoids exhibit an enhanced expression of cortical layer markers (TBR1 and CTIP2) under perfused cultures as compared to that under static cultures on a Petri dish, indicating the role of mechanical fluid flow in promoting brain organogenesis. The simple and robust brain organoids-on-a-chip system may open new avenues for various stem cell-based organoids engineering and its application in developmental biology and human disease studies.
机译:源自人诱导多能干细胞(HIPSCS)的自组织源自组织的脑有机体代表了一种用于造型脑发育和疾病的全体体外器官系统。然而,工程脑器有机体在肥大环境中有利于脑发展仍然具有挑战性。在这项工作中,我们展示了一种以受控方式使用器官芯片系统生成HIPSCS衍生的3D脑器有机体的新策略。该系统通过掺入三维(3D)基质胶,流体流动和组织的多细胞架构提供仿生脑微环境,其允许延长3D培养,原位神经分化和组织在单个装置上的脑器有机体组织。生成的脑器有机体在灌注的培养条件下显示明确定义的神经分化,区域化和皮质组织,这促进了早期人脑发育的关键特征。此外,与培养的培养物下,脑器有机体在灌注培养物下表现出皮质层标记(TBR1和CTIP2)的表达,与培养皿上的静态培养物相比,表明机械流体流动在促进脑动机发生中的作用。简单且强大的脑硬器有机体对芯片系统可以为各种干细胞的有机体工程开辟新的途径及其在发育生物学和人类疾病研究中的应用。

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  • 来源
    《RSC Advances》 |2018年第3期|共9页
  • 作者单位

    Chinese Acad Sci Dalian Inst Chem Phys Div Biotechnol 457 Zhongshan Rd Dalian 116023 Peoples R China;

    Chinese Acad Sci Dalian Inst Chem Phys Div Biotechnol 457 Zhongshan Rd Dalian 116023 Peoples R China;

    Chinese Acad Sci Dalian Inst Chem Phys Div Biotechnol 457 Zhongshan Rd Dalian 116023 Peoples R China;

    Chinese Acad Sci Dalian Inst Chem Phys Div Biotechnol 457 Zhongshan Rd Dalian 116023 Peoples R China;

    Chinese Acad Sci Dalian Inst Chem Phys Div Biotechnol 457 Zhongshan Rd Dalian 116023 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

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