E-Organoids: Functional Brain Organoids Co-grafted with Transparent Microthreads

多能干细胞技术的最新进展使得能够产生脑干细胞。 来自人外周组织的诱导多能干细胞的类器官。脑 类器官是由干细胞自组装的3D聚集体形成的， 细胞类型和层次模仿人类胚胎大脑。大脑类器官开放 研究大脑发育，神经元网络研究的前所未有的机会 功能障碍的潜在人类大脑疾病，并提供了一个实验系统， 测试和发现。脑类器官的体内移植提供了一种变革性的 可移植再生医学的未来应用的方法。虽然巨大的 近年来，类器官研究取得了突破性进展， 从根本上限制了它们的实用性和进一步发展， 人类大脑发育和紊乱的研究。第一个挑战是缺乏一个长期的 用于精确监测类器官的细胞和网络水平活动的功能界面 第二个挑战是缺乏自然的大脑微环境， 血管系统阻碍神经元的成熟并导致类器官核心处的细胞死亡。 该项目将通过创建具有无缝连接的电子类器官来克服这些挑战。 功能界面，将监测单个神经元和细胞群的活动，以及 为体外和体内的健康成熟提供氧气和营养。建议的E- 类器官将创建一个完整的平台，结合体内电生理学和双光子 用于人神经元活性的稳健和定量体内功能评价的显微镜 皮质类器官在细胞和网络水平。在未来，这项技术可以让 新药对人体发育和组织影响的系统研究 神经网络在发展过程中

Recent advances in pluripotent stem cell technology have enabled generation of cerebral organoids from induced pluripotent stem cells derived from human peripheral tissues. Cerebral organoids are formed by self-assembled, 3D aggregates generated from stem cells with different cell types and layers mimic the embryonic human brain. Cerebral organoids open up unprecedented opportunities for studying brain development, investigation of neuronal network dysfunctions underlying human brain diseases, and providing an experimental system for drug testing and discovery. In vivo transplantation of cerebral organoids offers a transformative approach for future applications of transplantable regenerative medicine. Although tremendous breakthroughs have been made in organoid research in the recent years, two key challenges fundamentally limit their utility and further development towards a complete model system for investigation of human brain development and disorders. The first challenge is lack of a chronic functional interface for precise monitoring cellular and network-level activity of the organoids with high precision and the second challenge is lack of the natural brain microenvironment and vasculature impeding maturation of neurons and causing cell death at the organoid core. This project will overcome these challenges by creating E-Organoids with a seamless functional interface that will monitor activity of individual neurons and cell populations as well as supply oxygen and nutrients for healthy maturation, in vitro and in vivo. The proposed E- Organoids will create a complete platform combining in vivo electrophysiology and 2-photon microscopy for robust and quantitative in vivo functional evaluation of neuronal activity of human cortical organoids at the cellular and network level. In the future, this technology could allow systematic investigation of effects of new drugs on development and organization of human neuronal networks during development.