Tel Aviv University research team successfully engineers world’s first 3D human spinal cord tissue transplant and gears up for human trials.
Scientists at TAU have hopes that those suffering paralysis could be able to walk again after lab-engineered stem cell spinal cord therapy demonstrated high rates of success in mice.
Longevity.Technology: Paralysis from spinal injury has a serious impact on lifespan and healthspan; spinal cord injury and degeneration can result in renal failure, pneumonia, pulmonary embolism, heart disease or septicaemia, as well as subsequent trauma, suicide and alcohol-related deaths also counted among major causes of death in patients. Publishing in Advanced Science, the Tel Aviv research team had an incredible 100% success rate in mice with acute paralysis, and not just in demonstrating a small amount of regeneration; the paralysed mice were able to walk again.
As well as injuries to the spine, this research has wider longevity implications; the nervous system and spinal cord are both affected by the aging process, losing nerve cells and experiencing atrophy. This breakdown of nerves has a knock-on effect, affecting the senses and causing reduced or lost reflexes or sensation that can lead to mobility impairment. Research shows that spinal grey matter is more likely to rupture the older it gets and becomes more fragile with age . If this decline could be reversed with therapy, it would guard against frailty, lack of mobility and loss of independence.
The TAU researchers engineered 3D human spinal cord tissues and implanted them in a lab models with long-term chronic paralysis and acute paralysis, demonstrating high rates of success in restoring walking abilities . Now, the team is preparing for the next stage of the study – clinical trials in human patients. The hope is that in just a few years, the engineered tissues will be implanted in paralysed individuals enabling them to stand up and walk once more.
How does fat help reverse a spinal injury?
“Our technology is based on taking a small biopsy of belly fat tissue from the patient,” explains Professor Tal Dvir whose research team led the study. “This tissue, like all tissues in our body, consists of cells together with an extracellular matrix comprising substances like collagens and sugars. After separating the cells from the extracellular matrix we used genetic engineering to reprogram the cells, reverting them to a state that resembles embryonic stem cells – namely cells capable of becoming any type of cell in the body .”
The researchers used omental stromal cells to create induced pluripotent stem cells (iPSCs); pluripotency means having the ability to become differentiated into any type of cell in the body – key when needing to recreate a functional neuronal network.
But the extracellular matrix did not go to waste; instead, the researchers used it to produce a personalised hydrogel that did not trigger an immune response or rejection after implantation, making it ideal for the purpose. The team then encapsulated the stem cells in the safe hydrogel, and, in a process that mimics the embryonic development of the spinal cord, turned the stem cells into 3D implants of neuronal networks containing motor neurons.
The human spinal cord implants were then implanted in two different groups of lab models: those who had only recently been paralysed (the acute model) and those who had been paralysed for a long time (the chronic model). The chronic model is equivalent to one year of paralysis in human terms. Following the implantation, 100% of the lab models with acute paralysis and 80% of those with chronic paralysis regained their ability to walk .
Stem cell therapy
The researchers discovered that the model animals underwent a rapid rehabilitation process, at the end of which they could walk quite well, and they claim (the researchers, not the mice) that this is the first instance in the world in which implanted engineered human tissues have generated recovery in an animal model for long-term chronic paralysis .
Although the 100% success rate in acute paralysis is the stuff of headlines, it is chronic paralysis which is the most relevant model for paralysis treatments in humans, as there is often a period of recovery and assessment undertaken before therapy can commence.
“Our goal is to produce personalized spinal cord implants for every paralyzed person, enabling regeneration of the damaged tissue with no risk of rejection,” says Professor Dvir.
With plans to develop and leverage the disruptive organ engineering technology developed in his lab, Professor Dvir teamed up with industry partners to establish Matricelf in 2019.
The company is now applying Dvir’s approach in the hope of making spinal cord implant treatments commercially available for those suffering from paralysis.
Professir Dvir, head of Sagol Center for Regenerative Biotechnology, is enthusiastic about the future of the technology. “We hope to reach the stage of clinical trials in humans within the next few years, and ultimately get these patients back on their feet,” he says. “The company’s preclinical program has already been discussed with the FDA. Since we are proposing an advanced technology in regenerative medicine, and since at present there is no alternative for paralyzed patients, we have good reason to expect relatively rapid approval of our technology .”