I-Corps: Brain Organoid Cell Products for Research and Therapeutic Applications

I-Corps项目更广泛的影响/商业潜力源于其潜在的应用，使人们能够更好地了解和治疗脑部疾病。去年，超过5000万美国成年人患有中枢神经系统疾病，如阿尔茨海默病、帕金森病、亨廷顿病、抑郁症和自闭症。特别是随着人口老龄化，神经退行性疾病，如阿尔茨海默病和帕金森病正在迅速增加。该项目进一步开发了一种创新技术，首次实现了可扩展的、具有成本效益的、符合gmp的人脑类器官的生成。这项技术将促进人脑类器官应用的发展，包括基础研究，包括药物发现和神经系统疾病的盘中疾病模型，以及临床应用，其中人脑类器官可能被开发为移植治疗细胞的来源。此外，这一技术进步促进了个性化医疗方法在治疗发展和脑细胞移植方面的进步。这个I-Corps项目的重点是人类大脑类器官的生产，作为基础科学发现、神经药物发现和各种人类大脑疾病的治疗性细胞生产的一种使能技术。该项目进一步开发了一种由诱导多能干细胞生成人脑类器官的改进方法。与先前描述的方法相比，该技术有几个优点，包括提高了类器官生产的简单性和效率，产品的一致性记录，仅使用化学定义的水凝胶基质和细胞培养基的生产方法，以及提高了制造的可扩展性。综合这些特点，第一次实现了一种商业上可行的脑类器官生产方法。该方法也适用于符合cgmp的制造，这使得从类器官开发治疗性细胞产品成为可能。

The broader impact/commercial potential of this I-Corps project derives from its potential applications that enable a better understanding of, and treatments for, brain disorders. Last year, over 50 million U.S. adults were afflicted by a central nervous system disease such as Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, and autism. Particularly as the population ages, neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are rapidly increasing. This project further develops an innovative technology that, for the first time, enables scalable, cost-effective, GMP-compliant generation of human brain organoids. The technology will facilitate the development of applications for human brain organoids both for basic research, including drug discovery and disease-in-the-dish modeling of neurological disorders, and clinical applications, where the human brain organoids may be developed as a source of therapeutic cells for transplantation. This technological advance, furthermore, promotes the advancement of personalized medicine approaches to both therapeutic development and brain cell transplantation.This I-Corps project is focused on the production of human brain organoids as an enabling technology for advancements in basic science discovery, neuropharmaceutical discovery, and therapeutic cell production for a wide variety of human brain disorders. The project further develops an improved method for the generation of human brain organoids from induced pluripotent stem cells. The technology has several advantages over previously described methods including improved simplicity and efficiency of organoid production, documented consistency of the product, production method using only a chemically defined hydrogel matrix and cell culture medium, and improved scalability of manufacturing. Taken together these features enable, for the first time, a commercially viable means of brain organoid production. The method is also amenable to cGMP-compliant manufacturing which enables the development of therapeutic cell products from the organoids.