Bundled Three-Dimensional Human Axon Tracts Derived from Brain Organoids.

Autor: Cullen DK; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, 3rd Floor, Silverstein Pavilion/3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: dkacy@pennmedicine.upenn.edu., Gordián-Vélez WJ; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, 3rd Floor, Silverstein Pavilion/3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA., Struzyna LA; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, 3rd Floor, Silverstein Pavilion/3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA; Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA., Jgamadze D; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, 3rd Floor, Silverstein Pavilion/3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA., Lim J; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, 3rd Floor, Silverstein Pavilion/3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA., Wofford KL; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, 3rd Floor, Silverstein Pavilion/3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA., Browne KD; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, 3rd Floor, Silverstein Pavilion/3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA., Chen HI; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, 3rd Floor, Silverstein Pavilion/3400 Spruce Street, Philadelphia, PA 19104, USA; Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. Electronic address: isaac.chen@uphs.upenn.edu.
Jazyk: angličtina
Zdroj: IScience [iScience] 2019 Nov 22; Vol. 21, pp. 57-67. Date of Electronic Publication: 2019 Oct 03.
DOI: 10.1016/j.isci.2019.10.004
Abstrakt: 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.
(Published by Elsevier Inc.)
Databáze: MEDLINE