With newly awarded funding from the National Science Foundation, researchers at the University of California, Irvine and the Keck School of Medicine of USC will seek to revolutionize the treatment of neurological diseases through intelligent biocomputing. The four-year, $2 million grant is part of NSF's Emerging Frontiers in Research and Innovation program, which funds cutting-edge science pushing the boundaries of human knowledge.
The premise of the UC Irvine-USC project is to combine engineering principles with stem cell research to treat damaged brain regions. The team's long-term goal is to restore motor functions to patients who have suffered brain damage from a stroke or experienced other neurological problems.
We believe that combining systems engineering and regenerative medicine might, with further research, help patients with neurological damage. The program will support the scientific research necessary to establish the foundations for future patient-treatment applications."
Dr. An Do, associate professor of neurology at UC Irvine, study's principal investigator
The idea behind the new research is to apply advanced biofabrication and adult stem cell technology to construct 3D neural networks in a way that emulates the self-learning mechanisms of the healthy brain. The team envisions that these intelligent networks can eventually integrate with the brain and body and be programmed to restore functions lost after an injury.
Do will oversee the project and lead bio-fabrication efforts. He will work with Zoran Nenadic, UC Irvine professor of biomedical engineering, who will handle the project's neural signal processing and neural network training processes. Hung Cao, an associate professor of electrical engineering at UC Irvine, will address the project's microfabrication and microelectronics engineering needs.
Leigh Turner, a professor of bioethics and public health at UC Irvine, will lead an exploration of the ethical, legal and social issues related to the project. Dr. Charles Liu, a professor of clinical neurological surgery, urology and surgery, and director of the USC Neurorestoration Center, will work directly with patients.
The UC Irvine-USC team has spent years developing brain-computer interfaces for neurorestoration, and in 2017 received an $8 million grant from NSF to expand that work. Since then, they have received recognition from both NSF and the Engineering in Medicine and Biology Society of the Institute of Electrical and Electronics Engineers.
Technologies converge
Stem cells hold promise for helping patients with brain and spinal cord damage. However, scientists have not yet been able to create networks of neural stem cells that are both functional and self-sustaining. Stem cells injected into damaged brain regions have the potential to grow and function but fail to generate any clinical benefits. The UCI and USC researchers believe that an engineering solution is needed to realize these goals.
First, the team will develop a method to print 3-D networks of neural stem cells in culture. These cells will have been gathered from adult donors and reprogrammed to a pluripotent state (capable of developing into different types of cells). Cultured stem cells can form neural networks and small "organoids" that are limited in size due to an inadequate supply of nutrients. Do and his colleagues plan to create artificial blood vessels that can help stem cell neural networks grow larger and thrive.
Next, the researchers aim to create a bidirectional connection between these cultured brain cells and the living human brain while research participants perform a behavioral task. These studies will take place at UC Irvine with able-bodied volunteers who will use their electroencephalogram (EEG) to interact with the cultured network.
The experiments will subsequently be expanded to epilepsy patients who have had electrodes implanted by the USC Epilepsy Care Consortium to manage their condition. The purpose of this research is to investigate whether cultured cells can learn and grow in response to brain signals – for instance, while a person performs a motor task with their hands – then send signals back to the brain in return. The clinical goal is that eventually, stroke patients may benefit from this research.
Intelligent biocomputing
Though this exploratory technology is still theoretical and many stages away from clinical practice, a successful outcome could lead to advances in the treatment of a broad range of neurological conditions. If the researchers can produce 3D neural networks that grow and learn, they plan to explore how powerful these intelligent biocomputers can become. The researchers plan to investigate whether they can perform just simple tasks, or if they are capable of complex functions such as logic and computing.
In the current project, the researchers will also use variety of research methods to address the ethical, legal, and social implications of such intelligent biological constructs.
This work is supported by the National Science Foundation grant 2422412.
Six other institutions received Emerging Frontiers in Research and Innovation grants. They are among the leading research universities in the U.S.: University of Michigan, University of Notre Dame, Virginia Tech, Harvard University, University of Maryland and Massachusetts Institute of Technology.
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