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Functional Integration of 3D-Printed Cerebral Cortical Tissue into a Brain Lesion

Authors :
Yongcheng Jin
Ellina Mikhailova
Ming Lei
Sally Cowley
Tianyi Sun
Xingyun Yang
Yujia Zhang
Kaili Liu
Daniel Catarino
Luana Campos Soares
Sara Bandiera
Francis G. Szele
Zoltan Molnar
Linna Zhou
Hagan Bayley
Publication Year :
2022
Publisher :
Cold Spring Harbor Laboratory, 2022.

Abstract

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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........1db545f81cb0594413e1403920a68bc8