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Issue 3, 2018, Issue in Progress
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Engineering stem cell-derived 3D brain organoids in a perfusable organ-on-a-chip system

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Abstract

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.

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

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Supplementary files

Article information


Submitted
23 Oct 2017
Accepted
23 Dec 2017
First published
05 Jan 2018

This article is Open Access

RSC Adv., 2018,8, 1677-1685
Article type
Paper

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

Y. Wang, L. Wang, Y. Guo, Y. Zhu and J. Qin, RSC Adv., 2018, 8, 1677
DOI: 10.1039/C7RA11714K

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    [Original citation] - Published by The Royal Society of Chemistry.

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