TY - JOUR
T1 - A Human Induced Pluripotent Stem Cell-Derived Tissue Model of a Cerebral Tract Connecting Two Cortical Regions
AU - Kirihara, Takaaki
AU - Luo, Zhongyue
AU - Chow, Siu Yu A.
AU - Misawa, Ryuji
AU - Kawada, Jiro
AU - Shibata, Shinsuke
AU - Khoyratee, Farad
AU - Vollette, Carole Anne
AU - Volz, Valentine
AU - Levi, Timothée
AU - Fujii, Teruo
AU - Ikeuchi, Yoshiho
N1 - Funding Information:
We thank Dr. Naoko Yoshie, Dr. Shintaro Nakagawa, and Mr. Kyungmo Sung for providing equipment and assistance for SEM analyses. We also thank Mr. Christian Felsner, Dr. Miles Pennington, and members of RCA-IIS design lab for discussion. This work was supported by Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research 17H05661 and 18K19903 (Y.I.), by CASIO Science Promotion Foundation (Y.I.), by Tanaka Memorial Foundation (Y.I.), and by a Grant for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) by AMED under the Grant Number JP18dm0207002 (S.S.).
Publisher Copyright:
© 2019 The Authors
PY - 2019/4/26
Y1 - 2019/4/26
N2 - Cerebral tracts connect separated regions within a brain and serve as fundamental structures that support integrative brain functions. However, understanding the mechanisms of cerebral tract development, macro-circuit formation, and related disorders has been hampered by the lack of an in vitro model. Here, we developed a human stem cell-derived model of cerebral tracts, which is composed of two spheroids of cortical neurons and a robust fascicle of axons linking these spheroids reciprocally. In a microdevice, two spheroids of cerebral neurons extended axons into a microchannel between the spheroids and spontaneously formed an axon fascicle, mimicking a cerebral tract. We found that the formation of axon fascicle was significantly promoted when two spheroids extended axons toward each other compared with axons extended from only one spheroid. The two spheroids were able to communicate electrically through the axon fascicle. This model tissue could facilitate studies of cerebral tract development and diseases.
AB - Cerebral tracts connect separated regions within a brain and serve as fundamental structures that support integrative brain functions. However, understanding the mechanisms of cerebral tract development, macro-circuit formation, and related disorders has been hampered by the lack of an in vitro model. Here, we developed a human stem cell-derived model of cerebral tracts, which is composed of two spheroids of cortical neurons and a robust fascicle of axons linking these spheroids reciprocally. In a microdevice, two spheroids of cerebral neurons extended axons into a microchannel between the spheroids and spontaneously formed an axon fascicle, mimicking a cerebral tract. We found that the formation of axon fascicle was significantly promoted when two spheroids extended axons toward each other compared with axons extended from only one spheroid. The two spheroids were able to communicate electrically through the axon fascicle. This model tissue could facilitate studies of cerebral tract development and diseases.
KW - Biodevices
KW - Neuroscience
KW - Techniques in Neuroscience
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U2 - 10.1016/j.isci.2019.03.012
DO - 10.1016/j.isci.2019.03.012
M3 - Article
AN - SCOPUS:85066260644
SN - 2589-0042
VL - 14
SP - 301
EP - 311
JO - iScience
JF - iScience
ER -
