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

E-类器官：与透明微丝共同移植的功能性大脑类器官

基本信息

批准号：
10002957
负责人：
Duygu Kuzum
金额：
$ 236.89万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-03-31
项目状态：
未结题

项目摘要

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.

多能干细胞技术的最新进展使大脑产生来自人类外周组织的诱导多能干细胞的器官。大脑器官是由自组装的3D聚集体形成的细胞类型和层模仿胚胎人脑。大脑器官开放研究大脑发育的前所未有的机会，神经元网络的研究人脑疾病的基础功能障碍，并为药物提供实验系统测试和发现。体内脑器官的体内移植提供了变革性的未来应用可再生医学的应用方法。虽然很大近年来，在器官研究中取得了突破，这是两个主要挑战从根本上限制了他们的效用，并进一步发展朝着完整的模型系统研究人脑发育和疾病。第一个挑战是缺乏慢性功能界面，用于精确监测器官的细胞和网络级活动精确度和第二个挑战是缺乏自然的大脑微环境和脉管系统阻碍神经元成熟并在器官核心引起细胞死亡。该项目将通过无缝创建电子甲素来克服这些挑战功能界面将监视单个神经元和细胞群的活动以及供应氧气和营养，以使健康成熟，体外和体内。提出的e- Organoid将创建一个完整的平台，结合体内电生理学和2-Photon 显微镜检查人类神经元活性的鲁棒和定量功能评估细胞和网络水平的皮质器官。将来，这项技术可以允许系统研究新药对人类发展和组织的影响开发过程中的神经元网络。