Researchers from the University of Oxford 3D printed human stem cells and created a two-layered brain tissue in a new study. When implanted into mouse brain slices, these cells demonstrated convincing structural and functional integration with the host tissue.
A ground-breaking technique developed by researchers at the University of Oxford could one day provide tailored repairs for people who have suffered brain injuries. For the first time, the researchers demonstrated that neural cells can be 3D printed to mimic the architecture of the cerebral cortex. The findings were published today in the journal Nature Communications.
3D Printed Human Stem Cells
The cells’ cortical structure was created using human induced pluripotent stem cells (hiPSCs), which have the ability to produce all cell types found in most human tissues. One significant advantage of using hiPSCs for tissue repair is that they can be easily derived from cells harvested from patients themselves, avoiding an immune response.
Using specific combinations of growth factors and chemicals, the hiPSCs were differentiated into neural progenitor cells for two different layers of the cerebral cortex. After suspending the cells in solution, two ‘bioinks’ were created, which were then printed to create a two-layered structure. The printed tissues retained their layered cellular architecture in culture for weeks, as evidenced by the expression of layer-specific biomarkers.
The Impact of the research
Brain injuries, such as those caused by trauma, stroke, and brain tumour surgery, typically result in significant damage to the cerebral cortex (the outer layer of the human brain), resulting in difficulties with cognition, movement, and communication. For example, approximately 70 million people worldwide suffer from traumatic brain injury (TBI) each year, with 5 millions of these cases being severe or fatal. There are currently no effective treatments for severe brain injuries, which has a serious impact on quality of life.
Tissue regenerative therapies, particularly those in which patients receive implants derived from their own stem cells, could be a promising future treatment option for brain injuries. However, there has been no way to ensure that implanted stem cells mimic the architecture of the brain until now.
This advance marks a significant step towards the fabrication of materials with the full structure and function of natural brain tissues. The work will provide a unique opportunity to explore the workings of the human cortex and, in the long term, it will offer hope to individuals who sustain brain injuries.
– Lead author Dr. Yongcheng Jin, Department of Chemistry, University of Oxford
Testing on Mice
When the printed tissues were implanted into mouse brain slices, they showed strong integration as evidenced by neural process projection and neuron migration across the implant-host boundary. The signalling activity of the implanted cells correlated with that of the host cells. This indicates that the human and mouse cells were communicating with one another, demonstrating both functional and structural integration.
“Our droplet printing technique provides a means to engineer living 3D tissues with desired architectures, which brings us closer to the creation of personalised implantation treatments for brain injury.”
– Senior author, Dr. Linna Zhou, Department of Chemistry, University of Oxford
The researchers plan to improve the droplet printing technique in order to create complex multi-layered cerebral cortex tissues that more realistically mimic the architecture of the human brain. These engineered tissues may be used in drug evaluation, brain development studies, and to improve our understanding of the basis of cognition, in addition to repairing brain injuries.
The new breakthrough builds on the team’s decade-long record of developing and patenting 3D printing technologies for synthetic tissues and cultured cells.
According to senior author Professor Hagan Bayley at the Department of Chemistry, University of Oxford, “This futuristic endeavour could only have been achieved by the highly multidisciplinary interactions encouraged by Oxford’s Martin School, involving both Oxford’s Department of Chemistry and the Department of Physiology, Anatomy and Genetics.”
The study ‘Integration of 3D-Printed Cerebral Cortical Tissue into an ex vivo Lesioned Brain Slice’ has been published in Nature Communications.
