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Three-dimensional human axon tracts derived from cerebral organoids

D. Kacy Cullen, Laura A. Struzyna, Dennis Jgamadze, Wisberty J. Gordián-Vélez, James Lim, Kathryn L. Wofford, Kevin D. Browne, H. Isaac Chen
doi: https://doi.org/10.1101/253369
D. Kacy Cullen
University of Pennsylvania;
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Laura A. Struzyna
University of Pennsylvania;
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Dennis Jgamadze
University of Pennsylvania;
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Wisberty J. Gordián-Vélez
University of Pennsylvania;
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James Lim
University of Pennsylvania;
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Kathryn L. Wofford
Drexel University
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Kevin D. Browne
University of Pennsylvania;
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H. Isaac Chen
University of Pennsylvania;
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  • For correspondence: isaac.chen@uphs.upenn.edu
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Abstract

Reestablishing cerebral connectivity is a critical part of restoring neuronal network integrity and brain function after trauma, stroke, and neurodegenerative diseases. Creating transplantable axon tracts in the laboratory is a novel strategy for overcoming the common barriers limiting axon regeneration in vivo, including growth-inhibiting factors and the limited outgrowth capacity of mature neurons in the brain. We describe the generation and phenotype of three-dimensional human axon tracts derived from cerebral organoid tissue. These centimeter-long constructs are encased in an agarose shell that permits physical manipulation and are composed of discrete cellular regions spanned by axon tracts and dendrites, mirroring the separation of grey and white matter in the brain. Features of cerebral cortex also are emulated, as evidenced by the presence of neurons with different cortical layer phenotypes. This engineered neural tissue has the translational potential to reconstruct brain circuits by physically replacing discrete cortical neuron populations as well as long-range axon tracts in the brain.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 25, 2018.
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Three-dimensional human axon tracts derived from cerebral organoids
D. Kacy Cullen, Laura A. Struzyna, Dennis Jgamadze, Wisberty J. Gordián-Vélez, James Lim, Kathryn L. Wofford, Kevin D. Browne, H. Isaac Chen
bioRxiv 253369; doi: https://doi.org/10.1101/253369
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Three-dimensional human axon tracts derived from cerebral organoids
D. Kacy Cullen, Laura A. Struzyna, Dennis Jgamadze, Wisberty J. Gordián-Vélez, James Lim, Kathryn L. Wofford, Kevin D. Browne, H. Isaac Chen
bioRxiv 253369; doi: https://doi.org/10.1101/253369

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