Novel strategies for promoting CNS repair through manipulation of FGF signalling and heparan sulphate proteoglycans

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One of the major limitations in the repair of the damaged CNS is scarring. This is induced in tissue after injury and involves the brain's major support cell (or glial cell), the astrocyte. One repair strategy for CNS injury is to transplant the patient's own glial cells (harvested from peripheral nerves) into the injury site to promote nerve regrowth. There are two possible candidates for cell transplantation, glia from the nose, olfactory ensheathing cells (OECs) and glia of peripheral nerves, Schwann cells. We have found that Schwann cells, but not OECs, induce astrocytic scarring both in experiments in dishes and animal models of injury. Our recent work has shown that Schwann cells secrete complex sugar molecules that enhance the action of specific growth factors, leading to scarring. OECs do not secrete the same sugar structures and, therefore, do not induce scarring, even though they secrete the growth factors known to influence scarring. We have recently developed a number of approaches. The aim of this application is to exploit this new information by developing and testing novel methods to interfere with complex sugar regulation of growth factor signalling in rat models. If successful, this work will lead to design of strategies to manipulate the inhibitory environment induced in humans after injury and promote CNS repair.