People who have been paralyzed may walk again after Israeli scientists successfully developed the first 3D human spinal cord tissue. Scientists have treated paralyzed mice by implanting these 3D printed spinal cord tissues in them. The mice regained the use of their legs, and they hope to start human trials in less than three years.
Researchers from Tel Aviv University’s Sagol Center for Regenerative Biotechnology, led by Prof. Tal Dvir, undertook the world-first, ground-breaking experiment. He was joined by researchers from the Shmunis School of Biomedicine and Cancer Research and the Department of Biomedical Engineering at TAU. The team at Dvir’s lab comprises Ph.D. student Lior Wertheim, Dr. Reuven Edri, and Dr. Yona Goldshmit. The research results were peer-reviewed and published in the journal Advanced Science. The aim is to “offer all paralyzed people hope that they may walk again.”
The experiment
In the study, the team engineered spinal cord tissue from human cells and implanted them into 15 mice with long-term paralysis. The mice were grouped into two: those who had been paralyzed for at least a year (chronic) and those who had been paralyzed lately (acute).
The mice with acute paralysis were able to walk again three months after the implantation, demonstrating considerable improvements over mice with acute paralysis who were left untreated. While the untreated mice did regain limited motor function over time, they had poorer coordination and a much lower capacity to apply pressure to the wounded foot, among other problems, than the mice who had the lab-grown spinal cord implanted.
Following the success of the acute injury phase, the researchers moved on to testing the same theory in mice with chronic paralysis, a more clinically relevant model due to the extent of irreversible damage to the spinal cord during the acute paralysis phase was still unknown.
The mice with chronic paralysis exhibited considerable improvement six weeks after the artificial spinal cord was implanted, demonstrating that the implant had successfully integrated into the body.
Ultimately, 80% of the mice in the test group could walk again.
Will the experiment be effective on humans?
Prof. Tal Dvir stated, “Millions of people worldwide are paralyzed due to spinal injury, and there is still no viable treatment for their disease.”
“If this works in humans, as we believe it will, it gives all paralyzed patients hope that they will be able to walk again.” He explained that while all of his mice had spinal implants made from the cells of three people if the technology is used in humans, each patient’s spine will be grown from their cells.
Dvir hopes that this will “allow regeneration of the damaged tissue with no rejection risk” and that it will eliminate the need to suppress recipients’ immune systems, as is the case with many transplants.
“Millions of people are paralyzed globally as a result of spinal damage, and there is still no viable cure for their condition,” Dvir stated.
“People who are paralyzed at an early age are doomed to spend the remainder of their life in a wheelchair, bearing all of the social, economic, and health-related expenses of paralysis.
We aim to find a solution and help them walk.”
To date, some scientific teams have performed experiments producing human-based stem cells and injecting them into animals’ spinal cords. But Dvir mentioned that the primary aim of the lab is to develop items of precise backbone engineered from human cells and transplant them.
Why haven’t we been able to heal spinal cord injuries?
A spinal cord injury, which can include damage to any section of the spinal cord or the nerves at the end of the spinal canal, can result in paralysis. These injuries can result in long-term alterations in strength, feeling, and other body processes, as well as long-term paralysis for which there is presently no therapy. Despite numerous previous initiatives worldwide to stimulate spontaneous or assisted regeneration at the site of damage, only limited success has been achieved.
Many existing experimental methods rely on transplanting different cells or biomaterials into the injury site. However, two issues threaten the treatment’s success: an immune reaction that causes the transplanted cells to be rejected and the implantation of fragmented cells that fail to establish a functioning network.
As a result, the researchers hypothesized that simulating embryonic development in a 3D dynamic environment using a specific spinal cord motor neuron differentiation protocol would provide cells with signals for appropriate regenerative tissue formation, healing the site, and reducing the risk of rejection.
The process starts with a small biopsy
“We separate fat cells from other components like sugars and collagen and then reprogram the cells using genetic engineering methods, so they can ‘become’ any cell in the body,” he stated.
“We put the cells in a substance made from non-cellular material extracted from the biopsy fat tissue, and we leave them there for 30 days to imitate how a spinal cord grows in an embryo. This generates spinal microneuron tissue, which we then transplant into animals that have been paralyzed for a long time.”
Clinical trials set to start soon
According to Dvir, Matricelf has been founded to bring the technology to clinical testing, which he believes to happen in the next two and a half years. While the work has involved mice, he underlined that the implants were generated from human cells, indicating that the research is already at an advanced stage.
“We’ve been putting human implants on the mice rather than mice implants, which means we won’t have to start over with human implants.
Instead, we understand how to prepare the implants for human use, which gives us hope that clinical trials will begin soon, “he stated.
The team at Dr. Dvir’s lab believes the new approach will apply to various diseases and traumas beyond spinal damage and are now testing it for Parkinson’s disease, brain trauma, myocardial infarction, and age-related macular degeneration.
