British researchers have discovered that long-chain sugars called heparan sulfates play a major role in the process of scar tissue formation following spinal cord injury.
It is known that scar tissue creates an impenetrable barrier to nerve regeneration, leading to the irreversible paralysis associated with spinal injuries. Scarring occurs due to the activation, change in shape, and stiffness of astrocytes – major nerve support cells in the spinal cord. One possible way to repair nerve damage is transplantation of support cells from peripheral nerves called Schwann cells.
The researchers, led by Dr Jennifer Higginson of the University of Glasgow’s Institute of Infection, Immunity and Inflammation, have found that these cells secrete heparan sulfate sugars, which promote scarring reactions and could reduce the effectiveness of nerve repair.
“Spinal injury is a devastating condition and can result in paralysis for life. The sugars we are investigating are produced by nearly every cell in the body, and are similar to the blood thinning drug heparin,” said Prof Jerry Turnbull of the University of Liverpool’s Institute of Integrative Biology, co-author of the study published in the Journal of Neuroscience.
Scientists showed that heparan sulfate sugars can over-activate protein growth factors that promote astrocyte scarring. Significantly, however, they found this over-activation could be inhibited by chemically modified heparins. These compounds could prevent the scarring reaction of astrocyte cells, opening up new opportunities for treatment of damaged nerve cells.
“We found that some sugar types promote scarring reaction, but remarkably other types, which can be chemically produced in the laboratory by modifying heparin, can prevent this in our cell models,” Prof Turnbull said. “Studies in animal cells are now needed, but the exciting thing about this work is that it could, in the future, provide a way of developing treatments for improving nerve repair in patients, using the body’s own Schwann cells, supplemented with specific sugars.”
“We had already shown that Schwann cells, identified as having the potential to promote nerve regrowth, induced scarring in spinal cord injury. Now that we know that they secrete these complex sugars, which lead to scarring, we have the opportunity to intervene in this process, and promote central nervous system repair,” explained senior author Prof Sue Barnett of the University of Glasgow’s Institute of Infection, Immunity and Inflammation.
The results have the potential to contribute to new strategies for manipulating the scarring process induced in spinal cord injury and improving the effectiveness of cell transplantation therapies in patients with this type of injury.
Bibliographic information: Jennifer R. Higginson et al. 2012. Differential Sulfation Remodelling of Heparan Sulfate by Extracellular 6-O-Sulfatases Regulates Fibroblast Growth Factor-Induced Boundary Formation by Glial Cells: Implications for Glial Cell Transplantation. The Journal of Neuroscience 32(45), 15902-15912; doi: 10.1523/JNEUROSCI.6340-11.2012