@article{894561b1252e4ef48088ab971f8d9b63,
title = "In-vitro engineered human cerebral tissues mimic pathological circuit disturbances in 3D",
abstract = "A method is developed to engineer cerebral tissues with intact 3D neuronal networks, mimicking neuropathological signatures such as the propagation of epileptiform discharges, using a multi-chambered tissue culture chip.In-vitro modeling of brain network disorders such as epilepsy remains a major challenge. A critical step is to develop an experimental approach that enables recapitulation of in-vivo-like three-dimensional functional complexity while allowing local modulation of the neuronal networks. Here, by promoting matrix-supported active cell reaggregation, we engineered multiregional cerebral tissues with intact 3D neuronal networks and functional interconnectivity characteristic of brain networks. Furthermore, using a multi-chambered tissue-culture chip, we show that our separated but interconnected cerebral tissues can mimic neuropathological signatures such as the propagation of epileptiform discharges.",
keywords = "HUMAN BRAIN-DEVELOPMENT, PLURIPOTENT STEM-CELLS, CORTICAL DEVELOPMENT, MODEL, NETWORKS",
author = "A. Saberi and A.P. Aldenkamp and N.A. Kurniawan and C.V.C. Bouten",
note = "Funding Information: We thank Jan de Boer, Jaap den Toonder, Anton de Louw, and Remco van der Hofstad for insightful discussions, Jurgen Bulsink for help with the fabrication of the iS3CC chip molds, Serena Buscone for support with immunohistochemical staining, Jos Broers and Florence van Tienen (Maastricht University) for sharing the hiPS cells, and Koen Pieterse (ICMS Animation Studio) for help with the illustrations used in this manuscript. The authors acknowledge support from the Dutch Research Council (grant OCENW.XS2.017, to N.A.K.), European Research Council (grant 851960, to N.A.K.), and the Netherlands{\textquoteright} Ministry of Education, Culture, and Science (Gravitation program “Materials-Driven Regeneration”, grant 024.003.013, to N.A.K. and C.V.C.B.). Funding Information: We thank Jan de Boer, Jaap den Toonder, Anton de Louw, and Remco van der Hofstad for insightful discussions, Jurgen Bulsink for help with the fabrication of the iS3CC chip molds, Serena Buscone for support with immunohistochemical staining, Jos Broers and Florence van Tienen (Maastricht University) for sharing the hiPS cells, and Koen Pieterse (ICMS Animation Studio) for help with the illustrations used in this manuscript. The authors acknowledge support from the Dutch Research Council (grant OCENW.XS2.017, to N.A.K.), European Research Council (grant 851960, to N.A.K.), and the Netherlands{\textquoteright} Ministry of Education, Culture, and Science (Gravitation program “Materials-Driven Regeneration”, grant 024.003.013, to N.A.K. and C.V.C.B.). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = mar,
day = "23",
doi = "10.1038/s42003-022-03203-4",
language = "English",
volume = "5",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Nature Publishing Group",
number = "1",
}