离体
诱导多能干细胞
神经科学
组织工程
大脑皮层
神经干细胞
祖细胞
脑组织
生物
生物医学工程
细胞生物学
干细胞
体内
胚胎干细胞
医学
基因
生物技术
生物化学
作者
Yongcheng Jin,Ellina Mikhailova,Ming Lei,Sally A. Cowley,Tianyi Sun,Xi Yang,Y. Zhang,Kaili Liu,Daniel Catarino da Silva,Luana Campos Soares,Sara Bandiera,Francis G. Szele,Zoltán Molnár,Linna Zhou,Hagan Bayley
标识
DOI:10.1038/s41467-023-41356-w
摘要
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 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.
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