An in vivo model of functional and vascularized human brain organoids.
An in vivo model of functional and vascularized human brain organoids.
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DOI：
10.1038/nbt.4127
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发表时间：
2018-06
影响因子：
46.9
通讯作者：
Gage FH
中科院分区：
文献类型：
--
作者：
Mansour AA;Gonçalves JT;Bloyd CW;Li H;Fernandes S;Quang D;Johnston S;Parylak SL;Jin X;Gage FH
将人类多能干细胞分化为被称为脑器官的小脑样结构，为模拟人类大脑发育和疾病提供了前所未有的机会。为了提供一种血管化和功能化的脑有机化合物体内模型，我们建立了一种将人脑有机化合物移植到成年小鼠脑内的方法。器官移植物表现为逐渐的神经元分化和成熟，胶质形成，小胶质细胞整合，轴突生长到宿主大脑的多个区域。活体双光子成像显示移植物中有功能的神经元网络和血管。最后，结合光遗传学的体内细胞外记录显示了移植物内神经元的活动，并提示移植物与宿主之间的功能性突触连接。这种人类神经器官和动物大脑中活体生理环境的结合可能有助于在生理条件下进行疾病建模。
Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.
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影响因子：
23.9
作者：
Bershteyn M;Nowakowski TJ;Pollen AA;Di Lullo E;Nene A;Wynshaw-Boris A;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.9
作者：
Assawachananont, Juthaporn;Mandai, Michiko;Okamoto, Satoshi;Yamada, Chikako;Eiraku, Mototsugu;Yonemura, Shigenobu;Sasai, Yoshiki;Takahashi, Masayo
通讯作者：
Takahashi, Masayo
影响因子：
64.8
作者：
Falkner, Susanne;Grade, Sofia;Huebener, Mark
通讯作者：
Huebener, Mark
影响因子：
8.8
作者：
Iefremova, Vira;Manikakis, George;Ladewig, Julia
通讯作者：
Ladewig, Julia