Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Stem Cell Reports. 2018 Apr 10;10(4):1222-1236. doi: 10.1016/j.stemcr.2018.02.012. Epub 2018 Mar 22.
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.
人类诱导多能干细胞来源的发育和神经退行性疾病模型在体外存在细胞不成熟的挑战。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，并允许不同细胞类型的共培养。脑微血管内皮细胞（BMEC）在早期发育过程中与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在很大程度上尚不清楚。为了研究这种相互作用和微培养的影响，我们从人类诱导多能干细胞中分离出脊髓运动神经元和 BMEC，并观察到与 96 孔板相比，器官芯片中钙瞬变功能和芯片特异性基因表达增加。在器官芯片中接种 BMEC 可导致血管-神经相互作用和特定基因激活，进一步增强神经元功能和类似于体内的特征。结果表明，血管系统对脊髓神经组织具有特定的成熟作用，并且器官芯片的使用可以使干细胞模型更接近体内条件。
