In a study at the University of California, San Diego (UCSD), and the U.S. Department of Veterans Affairs (VA) San Diego Healthcare System, researchers were able to regenerate what they say is “an astonishing degree” of axonal growth at the site of severe spinal cord injury (SCI) in rats. Their research revealed that early stage neurons have the ability to survive and extend axons to form new, functional neuronal relays across an injury site in the adult central nervous system (CNS). The study also proved that at least some types of adult CNS axons can overcome a normally inhibitory growth environment to grow over long distances. Stem cells across species exhibit these properties.
The work was published in the September 14 issue of the journal Cell.
The scientists embedded neural stem cells in a matrix of fibrin (a protein key to blood clotting that is already used in human neuron procedures) mixed with growth factors to form a gel. The gel was then applied to the injury site in rats with completely severed spinal cords.
“Using this method, after six weeks, the number of axons emerging from the injury site exceeded by 200-fold what had ever been seen before,” said Mark Tuszynski, MD, PhD, professor of neurosciences in the UCSD Department of Neurosciences and director of the UCSD Center for Neural Repair, who headed the study. “The axons also grew ten times the length of axons in any previous study and, importantly, the regeneration of these axons resulted in significant functional improvement.”
In addition, adult cells above the injury site regenerated into the neural stem cells, establishing a new relay circuit that could be measured electrically. To confirm that the mechanism underlying recovery was due to formation of new relays, when rats recovered, their spinal cords were re-transected above the implant. The rats lost motor function-confirming formation of new relays across the injury.
The grafting procedure resulted in significant functional improvement: On a 21-point walking scale, without treatment, the rats’ score was only 1.5; following the stem cell therapy, it rose to 7-a score reflecting the animals’ ability to move all joints of affected legs. Results were then replicated using two human stem cell lines, one already in human trials for amyotrophic lateral sclerosis (ALS). “We obtained the exact results using human cells as we had in the rat cells,” said Tuszynski.
According to the researchers, the study makes clear that early-stage neurons can overcome inhibitors present in the adult nervous system that normally work to maintain the elaborate CNS and to keep cells in the adult CNS from growing aberrantly.
Editor’s note: This story was adapted from materials provided by the University of California, San Diego, Health System.
