Bundled Three-Dimensional Human Axon Tracts Derived from Brain Organoids
| Autor: | Dennis Jgamadze, H. Isaac Chen, Kevin D. Browne, James Lim, D. Kacy Cullen, Kathryn L. Wofford, Wisberty J. Gordián-Vélez, Laura A. Struzyna |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
02 engineering and technology Biology Article White matter 03 medical and health sciences medicine Organoid Biological neural network Axon lcsh:Science Brain function Multidisciplinary Tissue Engineering Limiting Biological Sciences 021001 nanoscience & nanotechnology Phenotype 030104 developmental biology medicine.anatomical_structure nervous system Cerebral cortex lcsh:Q 0210 nano-technology Neuroscience |
| Zdroj: | iScience, Vol 21, Iss, Pp 57-67 (2019) iScience |
| ISSN: | 2589-0042 |
| Popis: | Summary 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. Graphical Abstract Highlights • 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 |
| Databáze: | OpenAIRE |
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