US researchers report successful implantation of neural stem cells directly into the area of spinal cord injury in mice. The grafts grew safely, filled the injury sites, and functioned like the existing animal neural network.
Scientists and doctors have long sought to use stem cells to restore functions lost as a result of spinal cord injury (SCI). In the United States, about 18,000 people suffer from this type of injury every year. Another 294,000 people suffer from complications of SCI, usually accompanied by varying degrees of paralysis or diminished physical function such as bladder control or difficulty breathing.
In a new study published August 5, 2020 in the journal Cell Stem Cell, scientists at the University of California (UC) San Diego School of Medicine report the successful implantation of highly specialized neural stem cell transplants directly into the area of spinal cord injury in mice. The article also describes how the grafts grew and filled in the injury sites, integrating with and copying the existing animal` neural network.
The first author of the study Steven Ceto, a researcher in Mark H. Tuszynski’s lab, MD, professor of neurosciences and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, said that up to this study, the neural stem cell transplants being developed in the lab were something like a black box.
Although previous research, including the published work of Tuszinski and colleagues, showed improved performance in animal models with SCI after neuronal stem cell transplantation, scientists didn’t know what mechanism underlies the recovery process.
“We knew that damaged host axons grew extensively into (injury sites), and that graft neurons in turn extended large numbers of axons into the spinal cord, but we had no idea what kind of activity was actually occurring inside the graft itself”, – said Ceto. “We didn’t know if host and graft axons were actually making functional connections, or if they just looked like they could be”.
Keto, Tuszynski and colleagues took advantage of the latest technological advances that allow researchers to both stimulate and record the activity of populations of neurons with specific genetic and structural properties using light, not electricity. This ensures confidence that the target neurons of the recipient and the graft are involved in the process and prevents potentially incorrect results due to the propagation of electric currents through the tissues.
Scientists found that even in the absence of a specific stimulus, spontaneous activity of transplant neurons is observed, which becomes correlated between large groups (clusters) of neighboring cells, as in the neural networks of a normal spinal cord.
When the researchers stimulated regenerating axons emerging from the animal brains, they found that some of the same spontaneously active clusters of transplant neurons responded stably. This indicates that these networks have established functional synaptic connections with areas that normally control movement. Sensory stimulation, such as light touching and pinching, also activated the transplanted neurons.
“We showed that we could turn on spinal cord neurons below the injury site by stimulating graft axons extending into these areas”, – said Ceto. “Putting all these results together, it turns out that neural stem cell grafts have a remarkable ability to self-assemble into spinal cord-like neural networks that functionally integrate with the host nervous system. After years of speculation and inference, we showed directly that each of the building blocks of a neuronal relay across spinal cord injury are in fact functional”.
Tuszinski said his team is currently working on several ways to improve the functional connectivity of stem cell transplants, such as arranging a graft topology with scaffolds to mimic the topology of a normal spinal cord, and using electrical stimulation to strengthen synapses between host and graft neurons.
“While the perfect combination of stem cells, stimulation, rehabilitation and other interventions may be years off, patients are living with spinal cord injury right now”, – Tuszynski said. “Therefore, we are currently working with regulatory authorities to move our stem cell graft approach into clinical trials as soon as possible. If everything goes well, we could have a therapy within the decade”.