Paralyzed rats with severed spinal cords are walking again, after Israeli scientists restored their nervous function and sensation using tissue engineering.
The researchers, from the Technion – Israel Institute of Technology and Tel Aviv University, developed a method to repair the damaged spinal cord based on tissue engineering and implantation of stem cells, taken from the oral mucosa membrane in the mouth near the gums. The rats regained sensation and control of their lower limbs, the team reports.
Spinal damage can lead to irreversible paralysis as a result of damage to the nerve cells responsible for communicating between other nerves. Even though significant progress has been made in rehabilitation, and other areas such as neuronal transplants and tissue engineering, the effects of a fully severed spinal cord have never been reversed before.
The research, which was published two weeks ago in the scientific journal Frontiers in Neuroscience, was led by Prof. Shulamit Levenberg, the dean of the faculty of biomedical engineering at the Technion, and Prof. Daniel Offen, of the medical school at Tel Aviv University and the head of the neuroscience lab. The lab research was headed by doctoral students Javier Ganz and Erez Shor.
“In the past, scientists have managed to rehabilitate and injured spinal cord using stem cells,” says Levenberg. “But this is the first time that stem cells restored feeling in limbs and complex motor ability, including fast walking, in a significant way, within only a few weeks.”
The researchers grew tissues to connect the two severed ends of the spinal cord of rats and produced new stem cells to restore sensitivity and motor function.
The research involved four main stages: first, they isolated mature stem cells from the mouth, choosing them because they are relatively easy to produce, said Levenberg.
The second stage was tissue engineering developed by Levenberg. The stem cells were placed on a three-dimensional scaffold, a sort of skeleton made of organic materials on which the tissue can develop. This scaffolding guides the direction of growth of the stem cells and neurons and gives the tissue its proper balance between flexibility and stiffness.
The third stage utilizes Offen’s research: infusing the cells with growth factors that lead them to secrete proteins that support the renewed production of neurons.
The fourth stage, after the engineered tissues are ready, is to implant them. Sixty days later the scaffold degrades and disappears.
The process restored the coordination, motor capabilities and ability to walk, among 42 percent of the test rats within three weeks.
On the accepted scale of functional rehabilitation, which ranges from 0 to 21, these rodents scored 17. Among the control group rats, who did not receive treatment, not a single one was able to walk.
This means the complex functioning required for walking, that includes moving, placing, feeling the limbs, and supporting weight and balance, was restored.
The implantation led to a gradual restoration of the severed spinal cord, regrowth of the neurons and cells and prevention of scar tissue, the scientists report. The rats began walking normally again, even without training or rehabilitation, said Levenberg.
It's early days: the road to human experiments is long. Levenberg is confident that these new methods could change lives, in the future.
"It is still not a medical breakthrough, but it is definitely a breakthrough in research,” said Dr. Nachshon Knoller, the director of spinal surgery at Sheba Medical Center at Tel Hashomer, who has worked with the researchers on the study. “All sorts of attempts have been made over the years to rehabilitate the spine. The studies in which implanting cells has been tried are not numerous. The combination of building a 3-D tissue in an attempt to rehabilitate the spine is completely new,” he added.
What is new in the study is that it produced results in situations where the spinal cord hade been completely severed and spontaneous healing is impossible, said Knoller.