Mammalian Neuroprogenitor Cells in Normal Embryonic, and in Normal and Injured Adult Spinal Cord: Procurement and Characterization

Zhou, F.C., Chai, H., Duguid, J., and Nelson, P.

Indiana University School of Medicine
Departments of Anatomy & Cell Biology
Neurosurgery and Neurology Indianapolis, IN 46202

      Neural progenitor cells have been found to exist in the mammalian nervous system. They are affluent during developmental stages but are quickly depleted as maturity is reached. In adulthood, a few brain regions still preserve a small fountain of progenitor cells for potential replenishment of nerve cells. The adult spinal cord is known to be poorly regenerative and maintains low neurogenesis activity. We found a rich supply of neuroprogenitor cells in the embryonic spinal cord, but a deprivation in the adult spinal cord. We report here that injury to spinal cord recruited a robust population of neural progenitor cells which are capable of infiltrating adult neural architecture. This study investigates the procurement and characterization of the progenitor cells from the injured adult spinal cord.

      Adult rat spinal cords were transected or untouched at the level of thoracic vertebrate. The spinal cord was divided into segments- local, proximal, and distal to the lesion. These segments were dissociated for screening progenitor cells with epidermal growth factor (EGF) and fibrous growth factor (FGF). A large yield of neurospheres was found in the proximal and distal segments, but a low yield in the local segment of the injured spinal cord; the number of neurospheres was also low from the segments of normal spinal cord at comparable vertebrate levels. These neurospheres, when sub-plated in adhesive substrate, expressed the neuroepithelial marker nestin and differentiated into glia and neurons. Injury may induce trophic molecule(s) which trigger the production of neuroprogenitor cells in the proximal and distal sites to the injury, however, the segment local to the injury may have also contained inhibitory cells or factors which prevented proliferation or regeneration of the spinal cells. These results indicate that (a) a progenitor cell pool can be activated, and (b) that injury to the spinal cord has diverse effects. The recruitment of a robust population of progenitor cells in spinal cord, which is known to be poor in regeneration and neurogenesis, may be achievable by harnessing these inhibitory and trophic elements.