An ependymal cell quest : identification and functional role of spinal cord neural stem cells

Sammanfattning: Few injuries have as profound and long-lasting consequences as spinal cord injury. The primary areas of impaired function typically include sensation, mobility, bladder, bowel and sexual function. The economic, social and personal effects can also be devastating. Today there is no cure available but the discovery of neural stem cells in the adult spinal cord has raised the hope for a treatment. It has, however, proven difficult to identify these stem cells and several different cell types including ependymal cells, astrocytes and oligodendrocyte progenitors have been proposed to function as neural stem or progenitor cells in the adult spinal cord. We assessed the generation of new cells from these cell populations under physiological conditions and after spinal cord injury. In Paper I, we identify ependymal cells as latent neural stem cells. They have in vitro stem cell potential and are multipotent in vivo after injury, giving rise to scarforming astrocytes and remyelinating oligodendrocytes. We also show thatoligodendrocyte progenitors and astrocytes are lineage restricted progenitors in theadult spinal cord. We offer an integrated view of how several different endogenous cell populations generate new cells under physiological and pathological conditions. Scar formation has traditionally been seen as an impediment to functional recovery after spinal cord injury. However, in Paper II, we show that scarring by ependymal cell-derived astrocytes is required to reinforce the tissue to prevent expansion of the lesion and further damage. We also identify ependymal cell progeny as a major source of neurotrophic support, and find substantial neuronal loss in the absence of this component of the scar tissue. In order to modify the endogenous stem cell response following an injury it is important to understand if all spinal cord ependymal cells have stem cell properties, or if this feature is limited to a subpopulation. In Paper III, we show that ependymal cells are functionally heterogeneous with proliferating progenitors and quiescent stem cells. The latent neural stem cell population in the adult spinal cord is made up of a small subpopulation of ependymal cells that are activated, proliferate and give rise to a large number of cells both in vitro and in response to injury. This thesis is an ependymal cell quest that provides new insights to the identity and function of a latent neural stem cell population residing in the center of the spinal cord.