Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development.
Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development.
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DOI：
10.1016/j.stemcr.2018.02.012
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发表时间：
2018-04-10
影响因子：
5.9
通讯作者：
Svendsen CN
中科院分区：
文献类型：
--
作者：
Sances S;Ho R;Vatine G;West D;Laperle A;Meyer A;Godoy M;Kay PS;Mandefro B;Hatata S;Hinojosa C;Wen N;Sareen D;Hamilton GA;Svendsen CN
人类干细胞衍生的发育和神经退行性疾病模型受到体外细胞不成熟的挑战。微工程器官芯片（或器官芯片）系统旨在模拟微体积细胞结构并实现不同细胞类型的共培养。脑微血管内皮细胞（BMEC）与发育早期的神经元共享共同的信号通路，但它们对人类神经元成熟的贡献很大程度上未知。为了研究微培养的这种相互作用和影响，我们从人类诱导多能干细胞中衍生出脊髓运动神经元和 BMEC，并观察到与 96 孔板相比，器官芯片中的钙瞬态功能和芯片特异性基因表达有所增加。在器官芯片中接种 BMEC 会导致血管-神经相互作用和特定基因激活，从而进一步增强神经元功能和体内样特征。结果表明，血管系统对脊髓神经组织具有特定的成熟作用，器官芯片的使用可以使干细胞模型更接近体内条件。 iPSC 衍生的神经和血管组织在器官芯片中相互作用 芯片培养增强神经元功能和信号传导 iPSC 衍生的脉管系统影响神经元发育和神经元脉管系统通路 在芯片上共培养的 BMEC 共培养激活体内脊髓发育基因 Sances 等人。将器官芯片技术与人类诱导多能干细胞来源的脊髓运动神经元相结合，研究器官芯片培养物的成熟效应。通过加入同样来自同一患者系的微血管细胞，作者显示了神经元功能的增强、血管神经元通路的复制以及类似于体内脊髓发育的特定基因激活。
Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs) share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition. iPSC-derived neural and vascular tissue interact in Organ-Chip Chip culture enhances neuron function and signaling iPSC-derived vasculature affects neuron development and neuron-vasculature pathways BMECs co-cultured on Chip co-culture activate in vivo spinal cord developmental genes Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development.
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影响因子：
16.6
作者：
Du, Zhong-Wei;Chen, Hong;Liu, Huisheng;Lu, Jianfeng;Qian, Kun;Huang, CindyTzu-Ling;Zhong, Xiaofen;Fan, Frank;Zhang, Su-Chun
通讯作者：
Zhang, Su-Chun
影响因子：
3.7
作者：
Gu, Chenghua;Giraudo, Enrico
通讯作者：
Giraudo, Enrico
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.2
作者：
Kurz, Haymo
通讯作者：
Kurz, Haymo
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