Functional integration of 3D-printed cerebral cortical tissue into a brain lesion

Engineering human tissue with diverse cell types and desired cellular architectures and functions is a considerable challenge. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricat...

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Main Authors: Jin, Y, Mikhailova, E, Lei, M, Cowley, S, Sun, T, Yang, X, Zhang, Y, Liu, K, Catarino, D, Soares, LC, Szele, FG, Bayley, H, Bandiera, S, Molnar, Z, Zhou, L
Format: Internet publication
Language:English
Published: 2022
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author Jin, Y
Mikhailova, E
Lei, M
Cowley, S
Sun, T
Yang, X
Zhang, Y
Liu, K
Catarino, D
Soares, LC
Szele, FG
Bayley, H
Bandiera, S
Molnar, Z
Zhou, L
author_facet Jin, Y
Mikhailova, E
Lei, M
Cowley, S
Sun, T
Yang, X
Zhang, Y
Liu, K
Catarino, D
Soares, LC
Szele, FG
Bayley, H
Bandiera, S
Molnar, Z
Zhou, L
author_sort Jin, Y
collection OXFORD
description Engineering human tissue with diverse cell types and desired cellular architectures and functions is a considerable challenge. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells (hiPSCs) were differentiated into upper- and deep-layer neural progenitors, which were then printed to form cerebral cortical tissues with a two-layer organization. The tissues showed layer-specific biomarker expression and developed an integrated network of processes. Implantation of the printed cortical tissues into mouse brain explants resulted in substantial implant-host integration across the tissue boundaries as demonstrated by the projection of processes, the migration of neurons and the appearance of correlated Ca2+ signals. The approach we have developed might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our approach might be applied in personalised implantation treatments that restore the cellular structure and function of a damaged brain by using 3D tissues derived from a patient’s own iPSCs.
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spelling oxford-uuid:68e984e9-4dad-4e29-b9a2-7c848287a23a2023-08-08T10:29:20ZFunctional integration of 3D-printed cerebral cortical tissue into a brain lesionInternet publicationhttp://purl.org/coar/resource_type/c_7ad9uuid:68e984e9-4dad-4e29-b9a2-7c848287a23aEnglishSymplectic Elements2022Jin, YMikhailova, ELei, MCowley, SSun, TYang, XZhang, YLiu, KCatarino, DSoares, LCSzele, FGBayley, HBandiera, SMolnar, ZZhou, LEngineering human tissue with diverse cell types and desired cellular architectures and functions is a considerable challenge. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells (hiPSCs) were differentiated into upper- and deep-layer neural progenitors, which were then printed to form cerebral cortical tissues with a two-layer organization. The tissues showed layer-specific biomarker expression and developed an integrated network of processes. Implantation of the printed cortical tissues into mouse brain explants resulted in substantial implant-host integration across the tissue boundaries as demonstrated by the projection of processes, the migration of neurons and the appearance of correlated Ca2+ signals. The approach we have developed might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our approach might be applied in personalised implantation treatments that restore the cellular structure and function of a damaged brain by using 3D tissues derived from a patient’s own iPSCs.
spellingShingle Jin, Y
Mikhailova, E
Lei, M
Cowley, S
Sun, T
Yang, X
Zhang, Y
Liu, K
Catarino, D
Soares, LC
Szele, FG
Bayley, H
Bandiera, S
Molnar, Z
Zhou, L
Functional integration of 3D-printed cerebral cortical tissue into a brain lesion
title Functional integration of 3D-printed cerebral cortical tissue into a brain lesion
title_full Functional integration of 3D-printed cerebral cortical tissue into a brain lesion
title_fullStr Functional integration of 3D-printed cerebral cortical tissue into a brain lesion
title_full_unstemmed Functional integration of 3D-printed cerebral cortical tissue into a brain lesion
title_short Functional integration of 3D-printed cerebral cortical tissue into a brain lesion
title_sort functional integration of 3d printed cerebral cortical tissue into a brain lesion
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