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

Yongcheng Jin, Ellina Mikhailova, Ming Lei, Sally A. Cowley, Tianyi Sun, Xingyun Yang, Yujia Zhang, Kaili Liu, Daniel Catarino da Silva, Luana Campos Soares, Sara Bandiera, Francis G. Szele (), Zoltán Molnár (), Linna Zhou () and Hagan Bayley ()
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Yongcheng Jin: University of Oxford
Ellina Mikhailova: University of Oxford
Ming Lei: University of Oxford
Sally A. Cowley: University of Oxford
Tianyi Sun: University of Oxford
Xingyun Yang: University of Oxford
Yujia Zhang: University of Oxford
Kaili Liu: University of Oxford
Daniel Catarino da Silva: University of Oxford
Luana Campos Soares: University of Oxford
Sara Bandiera: University of Oxford
Francis G. Szele: University of Oxford
Zoltán Molnár: University of Oxford
Linna Zhou: University of Oxford
Hagan Bayley: University of Oxford

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract 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 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.

Date: 2023
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DOI: 10.1038/s41467-023-41356-w

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