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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10002957
• 关键词: 3-Dimensional; Biological Models; Brain; Brain Diseases; Cell Death; Cells; Cerebrum; Chronic; Development; Disease; Drug Screening; Electrophysiology (science); Embryo; Evaluation; Future; Generations; Human; Human Activities; In Vitro; Individual; Investigation; Modeling; Monitor; Neurons; Nutrient; Organ; Organogenesis; Organoids; Oxygen; Patients; Peripheral; Pluripotent Stem Cells; Population; Regenerative Medicine; Research; System; Technology; Tissues; Transplantation; cell type; disease mechanisms study; drug discovery; drug testing; in vivo; induced pluripotent stem cell; innovation; network dysfunction; novel therapeutics; stem cell technology; stem cells; two photon microscopy

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脑细胞的生成成为可能 来自人类外周组织的诱导多能干细胞中的有机类化合物。大脑 有机化合物是由干细胞自组装而成的3D聚集体，具有不同的 细胞的类型和层次模仿了人类胚胎的大脑。大脑器官打开 研究大脑发育、研究神经网络面临前所未有的机遇 人类大脑疾病的潜在功能障碍，并为药物提供了一个实验系统 测试和发现。脑器官体内移植提供了一种变革性的 可移植再生医学未来应用的途径。尽管数量巨大 近年来，有机化合物研究取得了突破性进展，这是两个关键挑战 从根本上限制了它们的实用性，并进一步发展为一个完整的模型系统 研究人类大脑的发育和紊乱。第一个挑战是缺乏慢性 用于精确监测有机化合物的细胞和网络水平活动的功能接口 第二个挑战是缺乏自然的大脑微环境和 血管系统阻碍神经元的成熟并导致类器官核心的细胞死亡。 该项目将克服这些挑战，通过创建电子有机与无缝 功能界面，将监控单个神经元和细胞群体的活动以及 为体内和体外的健康成熟提供氧气和营养。建议的E- 有机化合物将创造一个完整的平台，将体内电生理学和双光子相结合 显微技术用于健壮、定量地评价人体神经活动的功能 在细胞和网络水平上的皮质有机体。在未来，这项技术可能会允许 新药对人体发育和组织影响的系统研究 发育过程中的神经元网络。