Integration of 3D-printed cerebral cortical tissue into an ex vivo lesioned brain slice
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Published:2023-10-04
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Jin Yongcheng, Mikhailova Ellina, Lei MingORCID, Cowley Sally A.ORCID, Sun Tianyi, Yang Xingyun, Zhang YujiaORCID, Liu Kaili, Catarino da Silva Daniel, Campos Soares Luana, Bandiera Sara, Szele Francis G.ORCID, Molnár ZoltánORCID, Zhou LinnaORCID, Bayley HaganORCID
Abstract
AbstractEngineering 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 Ca2+ 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’s own induced pluripotent stem cells.
Funder
Oxford University | Oxford Martin School, University of Oxford
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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