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CAREER:Engineering Brain-region-specific Organoids Derived from Human Stem Cells

职业：工程化源自人类干细胞的大脑区域特异性类器官

基本信息

批准号：
1652992
负责人：
Yan Li
金额：
$ 50.13万
依托单位：
Florida State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1652992&HistoricalAwards=false
关键词：
CAREER Engineering Brain region specific

项目摘要

PI: Li, YanProposal No: 1652992 The proposed work seeks to generate mini-brains (also called brain organoids) derived from human stem cells with defined structure and function that would mimic human brains. The brain organoids will provide an experimental platform that will enable discovery of novel interventions and pharmacological treatments for people with neurological disorders, such as Alzheimer's disease, Parkinson's disease, and more recently microcephaly in infants.Unavailability of access to human brain tissues limits the discovery of novel interventions and pharmacological treatments for people with neurological disorders, such as Alzheimer's disease, Parkinson's disease, and more recently microcephaly in infants. To address this critical need, the proposed work seeks to generate mini-brains (also called brain organoids) with defined structure and function that would mimic human brains. To achieve this, this project will utilize stem cell-based tissue engineering approach, leveraging the capability of stem cells to self-assemble into brain-like structure under suitable conditions. The proposed research provides a new approach for the understanding of brain tissue development, and a practical and clinically relevant platform for drug discovery and screening. Specifically, this project will generate and characterize homotypic and heterotypic brain-region-specific organoids derived from human stem cells; investigate the influence of extracellular matrix composition and remodeling on the formation of brain-like organoids; and, pattern brain tissue along rostral and caudal axis by modulating the Wnt signaling pathway. The novelty of the proposed research is that additional cell types are incorporated with induced pluripotent stem cell-derived neural spheroids and the extracellular matrices containing signaling molecules such as in Wnt pathway are provided to mimic spatial regulations that occur in human brain. In addition, the project will establish an interactive learning platform to form a bridge between academia and industry, while simultaneously reducing gender disparity and increasing the participation of minority students in engineering. The project will encourage African American and female students to pursue advanced career by recruiting them to participate in the proposed research and education. A broader goal of the proposed work is to establish a stem cell engineering research and education program that will attract underrepresented students for integrated multidisciplinary research and education. The education and outreach plan will accomplish the educational objectives by: establishing mentoring and research projects to attract female and minority students, enhancing Active Learning through Stem cell/Organoid engineering (ALSO) and digital platforms, and building an academia-industry pipeline to supply next-generation bioengineers.

主要研究者：Li，Yan提案编号：拟议的工作旨在产生来自人类干细胞的迷你大脑（也称为脑类器官），具有明确的结构和功能，可以模仿人类大脑。脑类器官将提供一个实验平台，使人们能够发现新的干预措施和药物治疗神经系统疾病的人，如阿尔茨海默病，帕金森病，最近在婴儿小头畸形。无法获得人类脑组织限制了发现新的干预措施和药物治疗神经系统疾病的人，如阿尔茨海默病，帕金森氏症，以及最近的婴儿小头畸形症。为了满足这一关键需求，拟议的工作旨在生成具有明确结构和功能的迷你大脑（也称为大脑类器官），以模仿人类大脑。为了实现这一目标，该项目将利用基于干细胞的组织工程方法，利用干细胞在适当条件下自组装成脑样结构的能力。这项研究为理解脑组织发育提供了一种新的方法，并为药物发现和筛选提供了一个实用和临床相关的平台。具体而言，该项目将产生和表征来自人类干细胞的同型和异型脑区域特异性类器官;研究细胞外基质组成和重塑对脑样类器官形成的影响;并通过调节Wnt信号通路沿沿着喙轴和尾轴对脑组织进行模式化。所提出的研究的新奇在于，将额外的细胞类型与诱导的多能干细胞衍生的神经球体结合，并提供含有信号分子（例如Wnt途径中的信号分子）的细胞外基质来模拟人脑中发生的空间调节。此外，该项目还将建立一个互动学习平台，在学术界和工业界之间架起一座桥梁，同时减少性别差距，增加少数民族学生对工程的参与。该项目将通过招募非裔美国人和女学生参加拟议的研究和教育，鼓励她们追求更高的职业。拟议工作的一个更广泛的目标是建立一个干细胞工程研究和教育计划，将吸引代表性不足的学生进行综合多学科研究和教育。教育和推广计划将通过以下方式实现教育目标：建立指导和研究项目，以吸引女性和少数民族学生，通过干细胞/类器官工程（ALSO）和数字平台加强主动学习，并建立一个生物工业管道，以提供下一代生物工程师。