Networked neural spheroid by neuro-bundle mimicking nervous system created by topology effect

Gi Seok Jeong, Joon Young Chang, Ji Soo Park, Seung A. Lee, Do Yeun Park, Junsung Woo, Heeyoung An, Changjoon Lee, Sang Hoon Lee

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

In most animals, the nervous system consists of the central nervous system (CNS) and the peripheral nervous system (PNS), the latter of which connects the CNS to all parts of the body. Damage and/or malfunction of the nervous system causes serious pathologies, including neurodegenerative disorders, spinal cord injury, and Alzheimer's disease. Thus, not surprising, considerable research effort, both in vivo and in vitro, has been devoted to studying the nervous system and signal transmission through it. However, conventional in vitro cell culture systems do not enable control over diverse aspects of the neural microenvironment. Moreover, formation of certain nervous system growth patterns in vitro remains a challenge. In this study, we developed a deep hemispherical, microchannel-networked, concave array system and applied it to generate three-dimensional nerve-like neural bundles. The deep hemicylindrical channel network was easily fabricated by exploiting the meniscus induced by the surface tension of a liquid poly(dimethylsiloxane) (PDMS) prepolymer. Neurospheroids spontaneously aggregated in each deep concave microwell and were networked to neighboring spheroids through the deep hemicylindrical channel. Notably, two types of satellite spheroids also formed in deep hemispherical microchannels through self-aggregation and acted as an anchoring point to enhance formation of nerve-like networks with neighboring spheroids. During neural-network formation, neural progenitor cells successfully differentiated into glial and neuronal cells. These cells secreted laminin, forming an extracellular matrix around the host and satellite spheroids. Electrical stimuli were transmitted between networked neurospheroids in the resulting nerve-like neural bundle, as detected by imaging Ca<sup>2+</sup> signals in responding cells.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalMolecular Brain
DOIs
Publication statusAccepted/In press - 2015 Mar 22

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Keywords

  • Deep hemicylindrical channel
  • Nerve-like structure
  • Neural bundle
  • Neural spheroid networking
  • Neurospheroid

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology

Cite this

Jeong, G. S., Chang, J. Y., Park, J. S., Lee, S. A., Park, D. Y., Woo, J., An, H., Lee, C., & Lee, S. H. (Accepted/In press). Networked neural spheroid by neuro-bundle mimicking nervous system created by topology effect. Molecular Brain, 1-12. https://doi.org/10.1186/s13041-015-0109-y