Journal Article

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

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

2023

Overview

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 2+ 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. Brain injuries can result in significant damage to the cerebral cortex, and restoring the cellular architecture of the tissue remains challenging. Here, the authors use a droplet printing technique to fabricate a simplified human cerebral cortical column and demonstrate its functionality and potential for future personalized therapy approaches.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/107 / 631/378/1689 / 631/61/490 / 631/61/54 / 639/166/985 / Biomarkers / Brain damage / Brain injury / Brain slice preparation / Brain stem / Calcium ions / Calcium signalling / Cell differentiation / Cerebral cortex / Cognition / Columns (structural) / Customization / Droplets / Drug development / Explants / Head injuries / Human tissues / Humanities and Social Sciences / Implantation / multidisciplinary / Neural networks / Neural stem cells / Neurons / Nutrients / Pluripotency / Science / Science (multidisciplinary) / Stem cells / Three dimensional printing / Tissue engineering