title: Networked neural spheroid by neuro-bundle mimicking nervous system created by topology effect.
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(2+) signals in responding cells.
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, 136-100, South Korea. arysu94@gmail.com.
authors.forename: Gi Seok
authors.initials: GS
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, 136-100, South Korea. jych102@gmail.com.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Chang
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, 136-100, South Korea. jisooo.park@gmail.com.|KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 136-701, South Korea. jisooo.park@gmail.com.
authors.forename: Ji Soo
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, 136-100, South Korea. seunga0128@naver.com.
authors.forename: Seung-A
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, 136-100, South Korea. ddosicky@gmail.com.
authors.forename: DoYeun
authors.initials: D
authors.lastname: Park
authors.affiliation: Center for Neural Science and WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea. junssam@gmail.com.|Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, South Korea. junssam@gmail.com.
authors.forename: Junsung
authors.initials: J
authors.lastname: Woo
authors.affiliation: Center for Neural Science and WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea. ahyheeyoung@gmail.com.
authors.forename: Heeyoung
authors.initials: H
authors.lastname: An
authors.affiliation: Center for Neural Science and WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, South Korea. cjl@kist.re.kr.|Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, South Korea. cjl@kist.re.kr.|KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 136-701, South Korea. cjl@kist.re.kr.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, 136-100, South Korea. dbiomed@korea.ac.kr.|KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 136-701, South Korea. dbiomed@korea.ac.kr.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D051381:Rats; D018874:Spheroids, Cellular / Q000166:cytology* / Q000187:drug effects; D013500:Surface Tension / Q000187:drug effects
chemical_list: D004129:Dimethylpolysiloxanes