Direct transplantation of stem cell precursors has been shown to result in beneficial therapeutic effects in animal models of spinal cord injury. This includes the use of precursor cells committed to developing along an oligodendroglial lineage. Experimental studies utilizing the application of recombinant Sonic Hedgehog (Shh) in models of rodent spinal cord injury have demonstrated proliferation of endogenous neural progenitor cells (reference 2, 3). Sonic Hedgehog is a molecule that is critically important in the development of the nervous system, particularly in the development of stem cells during embryogenesis. These cells have presumably arisen from a subpopulation of pluripotent cells lying dormant in the central nervous system of adult mammals and are induced to proliferate in the presence of Shh and spinal cord injury.
Models utilizing a demyelinating injury (similar to the injury to the white matter of the nervous system seen in Multiple Sclerosis, for example) in the dorsal column of adult rats have demonstrated increased numbers of progenitor cells in the grey and white matter of the spinal cord around the level of injury as well as around the central canal of the spinal cord (reference 1). In models of spinal cord contusion in adult rats, the addition of Shh to the site of injury has resulted in a strong trend toward improved functional recovery and axonal conduction when compared to control animals (reference 2, 3). The development of systemically administered Shh agonists allows study of the effects of chronic Shh activity within the nervous system following injury without requiring direct injection of the material into the spinal cord thereby avoiding the morbidity of such treatment (reference 3).
