Researchers used human neural stem cells to three-dimensionally print functional brain tissue that mimics the structure of the cerebral cortex, the outermost layer of the brain. This breakthrough technology promises to provide personalized repair for brain injuries.Our brains have delicate and complex structures that can be damaged by trauma, stroke, epilepsy and tumor removal surgery, resulting in difficulties with communication, movement and cognition. Implanted stem cells have the potential to regrow damaged brain tissue, but until now, using stem cells to rebuild brain structure has been difficult.
In a new study, researchers at the University of Oxford used 3D printing of human neural stem cells to create a double-layered brain tissue that was structurally and functionally integrated with the brain tissue of mice.
Linna Zhou, one of the corresponding authors of the study, said: "Our droplet printing technology provides a way to design living three-dimensional tissues with the desired structure, which brings us closer to creating personalized implant therapies for brain injuries."
Human induced pluripotent stem cells (hiPSCs) have great potential in tissue regeneration therapy. They are artificial stem cells derived from somatic cells that have been genetically reprogrammed to a state similar to embryonic stem cells, giving them the unique ability to differentiate into any cell type in the body.
In the current study, the researchers first differentiated hiPSCs into two types of neural progenitor cells, which are used to form the upper and deeper layers of the cerebral cortex. These layer-specific progenitor cells were used to create two bioinks and printed into layered tissues using three-dimensional droplet printing technology. The printed progenitor cells were allowed to mature and their growth and activity monitored over a week before the layered tissue was implanted into living mouse brain tissue.
The implanted tissue showed tight integration with the mouse brain cells, including the formation of neuronal processes -- the finger-like processes that conduct and transmit nerve signals -- and the migration of neurons across the boundary between the implant and the host. The implanted cells also displayed signaling activity associated with the host cells, indicating that the cells were communicating with each other and showed functional and structural integration.
Zoltán Molnár, another corresponding author of the study, said: "The development of the human brain is a subtle and delicate process with complex orchestration. It would be naive to think that we can reproduce the entire cellular development process in the laboratory. However, our 3D printing project shows that we have made substantial progress in controlling the fate and arrangement of human iPSCs to form the basic functional units of the cerebral cortex."
Since the human cerebral cortex has as many as six layers of nerve cells, the researchers plan to improve the three-dimensional droplet printing technology to create more complex multi-layered tissues to more realistically simulate brain structures. In addition to the printed tissue potentially being used to repair brain damage, they say it could also be used for drug testing, brain development research, and improving our understanding of cognition.
Jin Yongcheng, the first author of the study, said: "This progress marks an important step in our efforts to create materials with the complete structure and function of natural brain tissue. This work will provide a unique opportunity to explore the working principles of the human cerebral cortex, and in the long term, it will bring hope to brain-injured patients."
The research was published in the journal Nature Communications.