By James Gamble
Scientists have used a 3D printer to print human stem cells that could help repair brain injuries.
The researchers from Oxford University have successfully implanted the cells into the brains of mice.
The exciting advance has raised the prospect of the method being tailored for use in treating brain injuries in humans in the future, by essentially 3D printing brain cells.
In experiments, the implanted cells integrated into the animals’ brains both structurally and functionally.
The innovative University of Oxford study, published in the journal Nature Communications, marks the first time neural cells have been 3D printed to mimic the architecture of the cerebral cortex.
The research builds on a ten-year track record in producing and patenting 3D printing technologies for synthetic tissues and cultured cells.
The success of this latest project has increased hopes similar technology could one day be used to treat brain injuries.
Injuries to the brain, including those caused by trauma, stroke and surgery or tumors on the brain can typically result in damage to the cerebral cortex – the outer layer of the brain.
This can lead to difficulties in cognition – the process of acquiring knowledge and understanding through thought, experience, and the senses – as well as movement and communication.
Each year, around 70 million people across the globe suffer from traumatic brain injuries (TBI), with five million of those being severe or fatal.
But despite their significant toll on the human population, there are thus far no effective treatments for TBI, leading to serious impacts on the sufferer’s quality of life.
However, tissue regenerative therapies are seen as a promising route to treatment; especially those which incorporate implants derived from patients’ own stem cells.
But, up until now, no method has been able to ensure that implanted stem cells mimic the architecture of the brain.
In this latest study, researchers used 3D printing techniques to create a two-layered brain tissue using human neural stem cells.
When implanted into the brain slices of mice, these cells encouragingly showed convincing structural and functional integration with the host tissue.
The cortical structure was constructed from human induced pluripotent stem cells (hiPSCs), which have the potential to produce the cell types found in most human tissues.
A key advantage of using hiPSCs for tissue repair is that they can be easily derived from cells harvested from patients themselves; therefore not triggering an immune response.
The hiPSCs were differentiated into neural progenitor cells for two different layers of the cerebral cortex by using specific combinations of growth factors and chemicals.
The cells were then dipped in a solution to generate two ‘bioinks’, which were then printed to produce a two-layered structure.
The printed tissues maintained their layered cellular makeup for weeks, as indicated by the expression of layer-specific biomarkers.
Dr. Yongcheng Jin, a lead author of the study from the University of Oxford’s Department of Chemistry, excitedly explained: “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.”
When these printed tissues were implanted into brain slices in mice they displayed strong integration, demonstrated by the projection of neural processes and the movement of neurons across the boundary between the implanted and the host cells in the brain.
The implanted cells also showed signalling activity which correlated to that of the host cells – indicating that the human and mouse cells were communicating with each other and demonstrating functional as well as structural integration in the brain.
The research team now intend to further refine their printing technique to create complex, multi-layered cerebral cortex tissues that more realistically mimic the architecture of the human brain.
If successful, it is hoped that scientists may soon simply be able to print necessary brain cells from a patient’s own stem cells and implant them in the brain.
Besides their potential for repairing brain injuries, these engineered tissues might also have uses in drug evaluation, studies of brain development, and improvement of our understanding of the very basis of cognition.
Senior author Dr. Linna Zhou said: “Our droplet printing technique provides a means to engineer living 3D tissues with desired architectures, which brings us closer to the creation of personalized implantation treatments for brain injury.”
Associate Professor Francis Szele, from the University of Oxford’s Department of Physiology, Anatomy and Genetics and another senior author of the study, added: “The use of living brain slices creates a powerful platform for interrogating the utility of 3D printing in brain repair.
“It is a natural bridge between studying 3D printed cortical column development in vitro and their integration into brains in animal models of injury.”
Professor Zoltán Molnár, another senior author, said though the technology was not fully advanced yet, the study shows significant promise in treating brain injuries in the future.
“Human brain development is a delicate and elaborate process with a complex choreography,” he said.
“It would be naïve to think that we can recreate the entire cellular progression in the laboratory.
“Nonetheless, our 3D printing project demonstrates substantial progress in controlling the fates and arrangements of human iPSCs to form the basic functional units of the cerebral cortex.”
Produced in association with SWNS Talker