Yubing Sun (principal investigator) of the UMass Amherst Mechanical and Industrial Engineering (MIE) Department and Jun Yao (co-principal investigator) of the Electrical and Computer Engineering (ECE) Department have won a three-year, $564,510 award from the National Science Foundation (NSF) to create more lifelike neural organoids – or in vitro tissues that are artificially grown from stem cells, closely resemble parts of the human brain, and are excellent tools for studying that organ. Their NSF research will develop more realistic neural organoids that better mimic real human-brain structures and embody more accurate interactions among various regions of the brain. 

“Very briefly,” says Sun, “this project is to derive better brain organoids and track their development using our unique engineering tools.”

As the backstory to such research, a paper in Developmental Biology and reported by the National Institutes of Health National Library of Medicine explained that “Human organoids stand at the forefront of basic and translational research, providing experimentally tractable systems to study human development and disease. These stem-cell-derived, in vitro cultures can generate a multitude of tissue and organ types, including distinct brain regions and sensory systems. Neural-organoid systems have provided fundamental insights into molecular mechanisms governing cell-fate specification and neural-circuit assembly and serve as promising tools for drug discovery and understanding disease pathogenesis.” 

As Sun explains about the reason for their NSF project, “Neural organoids are excellent tools to study the development of human brains. However, they do not fully represent the brain structure. It is also difficult to record neuronal activities for a long time in neural organoids.”

Sun goes on to say that current, state-of-the-art, neural organoids are still restricted by their “lack of regionalization,” or the inability to mimic real human-brain structures realistically and simulate life-like interactions among those structures. What’s more, current neural organoids lack  the proper electrical hardware to monitor their development continuously over extended periods of time. 

“This project aims to transcend these key limitations,” says Yao, “by developing an engineered neural-organoid system that is properly regionalized and innervated with a tissue-like electronic mesh system capable of chronic monitoring and stimulation for improved studies of circuitry development in the neocortex.”  

To address all these challenges, Sun and Yao are pursuing three key objectives. First of all,  a new approach will be developed to derive neural organoids that better mimic brain structures. Those improved organoids will be assembled to represent true-to-life interactions between various brain regions. 

The second objective of this project is to incorporate tissue-like, ultra-flexible, mesh electrodes into these new organoids. Mesh electrodes are known to have minimal impacts on cells and can safely monitor the electrical activities of neurons on a continual basis. Previously, Sun, Yao, and their collaborators had successfully demonstrated the integration of this kind of tissue-like mesh system into in vitro cardiac tissue. Now they are confident that similar technology can be applied to the more sophisticated brain organoids for their advancement.

The third and last objective is to investigate if the act of applying electrical stimulation to neural organoids can significantly accelerate their maturation, which usually takes several months before they’re ready for research purposes. 

As Sun and Yao conclude, “Together, this project will lead to improved neural-organoid models and new knowledge of human-brain development.” 

The project will also support various educational and outreach activities, including new course development, undergraduate research projects, and paid internship programs. 

Sun and Yao add that “Highly motivated regional high-school, undergraduate, and graduate students from diverse backgrounds will have opportunities to engage in stem-cell research, which will facilitate the recruitment and retention of students in this exciting field.” (June 2024)

Article posted in Research