Controllable fusion of human brain organoids using acoustofluidics.
Controllable fusion of human brain organoids using acoustofluidics.
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DOI：
10.1039/d0lc01141j
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发表时间：
2021-02-23
期刊：
影响因子：
6.1
通讯作者：
Guo F
中科院分区：
文献类型：
--
作者：
Ao Z;Cai H;Wu Z;Ott J;Wang H;Mackie K;Guo F
人类类器官的融合在模拟组织发生和器官发生的生理和病理过程中具有广阔的应用前景。然而，目前的融合类器官模型面临着高异质性和可变再现性的挑战，这可能源于异质类器官的随机融合。因此，我们开发了一种简单而通用的声流方法，通过可控制的类器官空间排列来提高融合类器官模型的标准化。通过调节六边形声流体装置内的动态声场，我们可以以无接触、无标签和最小冲击的方式旋转、传输和融合一个类器官。作为模拟人类中脑到前脑中脑皮层通路发展的概念验证，我们通过神经上皮芽的可控排列将人类前脑类器官（hFOs）和人类中脑类器官（hMOs）声学融合。我们发现，组装后，hMO可以成功地将酪氨酸羟化酶神经元投射到hFO，同时兴奋性神经元的放电率和同步性增加。此外，我们发现我们的可控融合方法可以通过初始空间控制来调节集合体中神经元的投射（如范围、长度和密度）、投射成熟（如更高的发射频率和同步性）和神经祖细胞（NPC）的分裂。因此，我们的声流体方法可以作为一种无标签、无接触、高度生物相容性的工具，有效地组装类器官，促进基于类器官的疾病模型和组织工程的标准化和稳健性。
The fusion of human organoids holds promising potential in modeling physiological and pathological processes of tissue genesis and organogenesis. However, current fused organoid models face challenges of high heterogeneity and variable reproducibility, which may stem from the random fusion of heterogeneous organoids. Thus, we developed a simple and versatile acoustofluidic method to improve the standardization of fused organoid models via a controllable spatial arrangement of organoids. By regulating dynamic acoustic fields within a hexagonal acoustofluidic device, we can rotate, transport, and fuse one organoid with another in a contact-free, label-free, and minimal-impact manner. As a proof-of-concept to model the development of the human midbrain-to-forebrain mesocortical pathway, we acoustically fused human forebrain organoids (hFOs) and human midbrain organoids (hMOs) with the controllable alignment of neuroepithelial buds. We found that post-assembly, hMO can successfully project tyrosine hydroxylase neurons towards hFO, accompanied by an increase of firing rates and synchrony of excitatory neurons. Moreover, we found that our controllable fusion method can regulate neuron projection (e.g., range, length, and density), projection maturation (e.g., higher firing rate and synchrony), and neural progenitor cell (NPC) division in the assembloids via the initial spatial control. Thus, our acoustofluidic method could serve as a label-free, contact-free, and highly biocompatible tool to effectively assemble organoids and facilitate the standardization and robustness of organoid-based disease models and tissue engineering.
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影响因子：
46.9
作者：
Lancaster MA;Corsini NS;Wolfinger S;Gustafson EH;Phillips AW;Burkard TR;Otani T;Livesey FJ;Knoblich JA
通讯作者：
Knoblich JA
影响因子：
44.1
作者：
Friend, James;Yeo, Leslie Y.
通讯作者：
Yeo, Leslie Y.
影响因子：
29.4
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Chen, Pu;Luo, Zhengyuan;Gueven, Sinan;Tasoglu, Savas;Ganesan, Adarsh Venkataraman;Weng, Andrew;Demirci, Utkan
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Demirci, Utkan
影响因子：
4.6
作者：
Kasendra M;Tovaglieri A;Sontheimer-Phelps A;Jalili-Firoozinezhad S;Bein A;Chalkiadaki A;Scholl W;Zhang C;Rickner H;Richmond CA;Li H;Breault DT;Ingber DE
通讯作者：
Ingber DE
影响因子：
64.8
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
通讯作者：
Paşca SP