TY - JOUR
T1 - Networked neural spheroid by neuro-bundle mimicking nervous system created by topology effect
AU - Jeong, Gi Seok
AU - Chang, Joon Young
AU - Park, Ji Soo
AU - Lee, Seung A.
AU - Park, Doyeun
AU - Woo, Junsung
AU - An, Heeyoung
AU - Lee, C. Justin
AU - Lee, Sang Hoon
N1 - Funding Information:
This work was supported by the Industrial Strategic Technology Development Program, the Ministry of Trade, Industry & Energy (MI, Korea) (Project No.10041923) and Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2012M3C7A1055410).
Publisher Copyright:
© 2015 Jeong et al.
PY - 2015/3/22
Y1 - 2015/3/22
N2 - 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, concavearray 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 Ca2+ signals in responding cells.
AB - 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, concavearray 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 Ca2+ signals in responding cells.
KW - Deep hemicylindrical channel
KW - Nerve-like structure
KW - Neural bundle
KW - Neural spheroid networking
KW - Neurospheroid
UR - http://www.scopus.com/inward/record.url?scp=84928122847&partnerID=8YFLogxK
U2 - 10.1186/s13041-015-0109-y
DO - 10.1186/s13041-015-0109-y
M3 - Article
C2 - 25888468
AN - SCOPUS:84928122847
SN - 1756-6606
VL - 8
JO - Molecular Brain
JF - Molecular Brain
M1 - 17
ER -