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3D bioprinting of human neural tissues with functional connectivity
Cell Stem Cell ( IF 23.9 ) Pub Date : 2024-02-01 , DOI: 10.1016/j.stem.2023.12.009
Yuanwei Yan , Xueyan Li , Yu Gao , Sakthikumar Mathivanan , Linghai Kong , Yunlong Tao , Yi Dong , Xiang Li , Anita Bhattacharyya , Xinyu Zhao , Su-Chun Zhang

Probing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. We developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter. The printed neuronal progenitors differentiate into neurons and form functional neural circuits within and between tissue layers with specificity within weeks, evidenced by the cortical-to-striatal projection, spontaneous synaptic currents, and synaptic response to neuronal excitation. Printed astrocyte progenitors develop into mature astrocytes with elaborated processes and form functional neuron-astrocyte networks, indicated by calcium flux and glutamate uptake in response to neuronal excitation under physiological and pathological conditions. These designed human neural tissues will likely be useful for understanding the wiring of human neural networks, modeling pathological processes, and serving as platforms for drug testing.

中文翻译:

具有功能连接的人体神经组织 3D 生物打印

由于缺乏可靠的人类神经组织来进行神经回路的动态功能评估,探索人类神经网络如何运作受到阻碍。我们开发了一个 3D 生物打印平台,使用商业生物打印机将具有定义的人类神经细胞类型的组织组装到所需的尺寸。打印的神经元祖细胞在数周内分化为神经元,并在组织层内和组织层之间形成具有特异性的功能性神经回路,皮层到纹状体的投射、自发突触电流和对神经元兴奋的突触反应证明了这一点。印刷的星形胶质细胞祖细胞发育成具有复杂过程的成熟星形胶质细胞,并形成功能性神经元-星形胶质细胞网络,这通过生理和病理条件下响应神经元兴奋的钙通量和谷氨酸摄取来表明。这些设计的人类神经组织可能有助于理解人类神经网络的连接、模拟病理过程以及作为药物测试平台。
更新日期:2024-02-01
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