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.
