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Published, Version of Record (VoR)CC BY-NC-ND V4.0, Open
Journal article
Bundled Three-Dimensional Human Axon Tracts Derived from Brain Organoids
iScience, v 21
22 Nov 2019
PMID: 31654854
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 an unexplored 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, phenotype, and connectivity of constrained three-dimensional human axon tracts derived from brain organoids. 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, mirroring the separation of cerebral gray and white matter. Features of cerebral cortex also are emulated, as evidenced by the presence of neurons with different cortical layer phenotypes. This engineered neural tissue represents a first step toward potentially reconstructing brain circuits by physically replacing neuronal populations and long-range axon tracts in the brain.
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•Transplantable 3D axon tracts are tissue engineered from human brain organoids•Growth of organoid axons in a hydrogel column is enhanced compared with planar culture•Organoids within engineered columns can maintain a laminar cortical architecture•Functional connectivity across the construct is demonstrated using calcium imaging
Biological Sciences; Neuroscience; Tissue Engineering
Metrics
Details
- Title
- Bundled Three-Dimensional Human Axon Tracts Derived from Brain Organoids
- Creators
- D. Kacy Cullen - Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USAWisberty J. Gordián-Vélez - Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USALaura A. Struzyna - Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USADennis Jgamadze - University of PennsylvaniaJames Lim - University of PennsylvaniaKathryn L. Wofford - University of PennsylvaniaKevin D. Browne - University of PennsylvaniaH. Isaac Chen - University of Pennsylvania
- Publication Details
- iScience, v 21
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000498899800005
- Scopus ID
- 2-s2.0-85073608343
- Other Identifier
- 991019176796504721
UN Sustainable Development Goals (SDGs)
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- Web of Science research areas
- Neurosciences