24-07-08(19:01:44)
Authors:
Fanie Barnabé-Heider
Institutions:
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden
Title of abstract : Identification and characterization of stem/progenitor cells upon spinal cord injury
Abstract text:
Spinal cord injury results in permanent functional impairment due to limited regenerative capacity. Improved functional recovery has been reported upon adult spinal cord-derived neural stem cells suggesting that recruitment of endogenous stem cells could represent a novel therapeutic approach. However, the identity of adult spinal cord stem cells in vivo and their reaction to injury has been difficult to establish. We generated transgenic mouse lines enabling fate mapping of ependymal cells using promoters of two cell-type specific genes, FoxJ1 and Nestin to drive the expression of the tamoxifen-regulated CreERT2 protein. Upon tamoxifen treatment, both transgenic lines have specific recombination in the cells surrounding the central canal. This cell population is morphologically, but not molecularly, heterogeneous. When assessed in vitro, the labeled cell population contains the vast majority of stem cell activity of the adult spinal cord. In vivo studies show that ependymal cells are activated in response to injury: they proliferate, give rise to progeny which migrate to the injury, and constitute a significant cell population at the lesion site even after several months. The central canal cell-derived progeny loses some ependymal cell features and undertakes an astrocytic phenotype, including scar-forming astrocytes, and interestingly, oligodendrocytes. Preliminary analysis of the parenchymal progenitor Olig2-CreER transgenic line, suggests that this second spinal cord progenitor pool is differently and complementary recruited by injury. Characterization and direct in vivo comparison of these stem/progenitor populations should lead to therapeutically relevant findings for the treatment of spinal cord injuries.
