Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice

<p>Engineering human tissue with diverse cell types and architectures remains challenging. 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. How...

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Huvudupphovsmän: Jin, Y, Mikhailova, E, Lei, M, Zhou, L, Bayley, H, Cowley, SA, Sun, T, Yang, X, Zhang, Y, Liu, K, Catarino da Silva, D, Campos Soares, L, Bandiera, S, Szele, FG, Molnár, Z
Materialtyp: Journal article
Språk:English
Publicerad: Springer Nature 2023
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author Jin, Y
Mikhailova, E
Lei, M
Zhou, L
Bayley, H
Cowley, SA
Sun, T
Yang, X
Zhang, Y
Liu, K
Catarino da Silva, D
Campos Soares, L
Bandiera, S
Szele, FG
Molnár, Z
author_facet Jin, Y
Mikhailova, E
Lei, M
Zhou, L
Bayley, H
Cowley, SA
Sun, T
Yang, X
Zhang, Y
Liu, K
Catarino da Silva, D
Campos Soares, L
Bandiera, S
Szele, FG
Molnár, Z
author_sort Jin, Y
collection OXFORD
description <p>Engineering human tissue with diverse cell types and architectures remains challenging. 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 are differentiated into upper- and deep-layer neural progenitors, which are then printed to form cerebral cortical tissues with a two-layer organization. The tissues show layer-specific biomarker expression and develop a structurally integrated network of processes. Implantation of the printed cortical tissues into ex vivo mouse brain explants results in substantial structural implant-host integration across the tissue boundaries as demonstrated by the projection of processes and the migration of neurons, and leads to the appearance of correlated Ca<sup>2+</sup>&nbsp;oscillations across the interface. The presented approach might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our methodology offers a technical reservoir for future personalized implantation treatments that use 3D tissues derived from a patient&rsquo;s own induced pluripotent stem cells.</p>
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spelling oxford-uuid:4e6e97f3-9b5f-4c35-a56f-2a8b5f5a2cfd2024-02-27T07:28:31ZIntegration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain sliceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4e6e97f3-9b5f-4c35-a56f-2a8b5f5a2cfdEnglishSymplectic ElementsSpringer Nature2023Jin, YMikhailova, ELei, MZhou, LBayley, HCowley, SASun, TYang, XZhang, YLiu, KCatarino da Silva, DCampos Soares, LBandiera, SSzele, FGMolnár, Z<p>Engineering human tissue with diverse cell types and architectures remains challenging. 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 are differentiated into upper- and deep-layer neural progenitors, which are then printed to form cerebral cortical tissues with a two-layer organization. The tissues show layer-specific biomarker expression and develop a structurally integrated network of processes. Implantation of the printed cortical tissues into ex vivo mouse brain explants results in substantial structural implant-host integration across the tissue boundaries as demonstrated by the projection of processes and the migration of neurons, and leads to the appearance of correlated Ca<sup>2+</sup>&nbsp;oscillations across the interface. The presented approach might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our methodology offers a technical reservoir for future personalized implantation treatments that use 3D tissues derived from a patient&rsquo;s own induced pluripotent stem cells.</p>
spellingShingle Jin, Y
Mikhailova, E
Lei, M
Zhou, L
Bayley, H
Cowley, SA
Sun, T
Yang, X
Zhang, Y
Liu, K
Catarino da Silva, D
Campos Soares, L
Bandiera, S
Szele, FG
Molnár, Z
Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
title Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
title_full Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
title_fullStr Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
title_full_unstemmed Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
title_short Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
title_sort integration of 3d printed cerebral cortical tissue into an ex vivo lesioned brain slice
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