RT Journal Article
SR Electronic
T1 Three-dimensional human axon tracts derived from cerebral organoids
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 253369
DO 10.1101/253369
A1 D. Kacy Cullen
A1 Laura A. Struzyna
A1 Dennis Jgamadze
A1 Wisberty J. Gordián-Vélez
A1 James Lim
A1 Kathryn L. Wofford
A1 Kevin D. Browne
A1 H. Isaac Chen
YR 2018
UL http://biorxiv.org/content/early/2018/01/24/253369.abstract
AB 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.eTOC Blurb Restoring axonal connectivity after brain damage is crucial for improving neurological and cognitive function. Cullen, et al. have generated anatomically inspired, three-dimensional human axon tracts projecting from cerebral organoids in a transplantable format that may facilitate the reconstruction of large-scale brain circuits.HighlightsA neural tissue engineering approach is applied to human cerebral organoids.Three-dimensional axon tracts are generated in a transplantable format.The growth characteristics of the engineered axons are examined.The cellular phenotypes of the organoid tissue and axons are characterized.