Researchers invent way to determine optimal conditions for spinal cord nerve regen in lab animals

Mayo Clinic researchers have created a method for measuring the growth of new spinal cord nerve fibers in rats, an advance that allows them to quickly determine nerve regeneration rate and what variables in the nerve-growth environment best support it.
The finding is important because it is a first step in laboratory animal models that will help scientists refine and improve nerve repair and regrowth in spinal cord injuries. While much basic science remains to be completed, this path of discovery could possibly lead one day to new therapies to reverse paralysis in human patients who have suffered complete spinal cord injury. The findings will be presented April 30 in San Francisco at the American Academy of Neurology annual meeting.

Significance of the Mayo Clinic Finding

This new regrowth measurement method and evaluating conditions of the spinal microenvironment in which regrowth occurs extend earlier Mayo Clinic research. In the earlier research the team successfully regenerated healthy spinal nerve endings of paralyzed rats using an implantable scaffolding. The scaffolding is referred to as a “biodegradable spinal graft.”

Mayo Clinic’s experimental scaffolding consists of several innovations. It uses polymer chemistry to create a biodegradable material that can be molded, through microfabrication techniques, to make implantable, trellis-like scaffolding that both supports and guides new nerve fibers. It does this by providing channels through which the axons (nerve endings) grow.

The new measurement method shows that the scaffolding not only supports axon regeneration when seeded with cells that stimulate regrowth, but that it can quantify axon growth under different experimental conditions. “Knowing what conditions favor regrowth — or retard it — enables researchers to design a maximally efficient system for achieving the best regrowth,” says Anthony Windebank, M.D., neurologist, molecular neuroscientist and joint principal investigator.

“We feel that this research program will make a contribution toward a solution to the spinal cord injury problem,” adds Michael Yaszemski, M.D., Ph.D., orthopedic spinal surgeon and chemical engineer.

The determination of the effectiveness of the scaffolding is important because other surgical attempts to regenerate nerve growth do not direct and support the growth, so crucial connections needed to restore the damaged nerve are not always made. Without these connections, electrical impulses that coordinate movement cannot be conducted and paralysis cannot be reversed.

Background

Both synthetic and biological axon growth-guidance channels have been studied. Biological channels usually consisted of grafts of nerves from the peripheral nervous system. Synthetic channels included various biocompatible materials. The channels have been filled with different types of cells to determine the most viable “supporting cells” for creating nerve regrowth. These include: Schwann cells, olfactory ensheathing glia, neural stem cells and others.

But researchers lacked an effective way to compare the ability of different cell types to support axonal regeneration. Then they discovered that the scaffolding also can be used as a kind of “measuring stick” to quantify nerve regrowth.

The Experiment

To test this idea, researchers loaded 3 mm-long scaffolds with several different types of supporting cells to generate new nerves. They then surgically inserted each into identical 3 mm-long gaps made in rat spinal cords. One month after implantation, four to six spinal cords and scaffolds were harvested from the rats, and systematically analyzed and compared, from nose to tail section. Other conditions were altered in the regrowth environment and tracked to determine their effects on nerve regrowth. A researcher with no knowledge of which cell type was in each scaffold, or which environment had been altered, then counted axon regrowth.

Results and Conclusions

Results varied. Some cell types supported no growth at the midpoint of the scaffold; others supported considerable growth. Researchers conclude that the biodegradable particular scaffolds can successfully be seeded with certain cells and support axon regrowth throughout the length of the scaffold. In addition, they believe axon counting after one month is an effective way to distinguish the effects of alterations in the microenvironment of axon regeneration. These findings will help lead researchers to the next step — optimizing conditions of the microenvironment in which nerve regrowth occurs. Further studies will then be needed to determine if nerve function improves with optimal growth.