Adult spinal cord stem cells generate neurons after transplantation in theadult dentate gyrus

The adult rat spinal cord contains cells that can proliferate and different iate into astrocytes and oligodendroglia in situ. Using clonal and subclona l analyses we demonstrate that, in contrast to progenitors isolated from th e adult mouse spinal cord with a combination of growth factors, progenitors isolated from the adult rat spinal cord using basic fibroblast growth fact or alone display stem cell properties as defined by their multipotentiality and self-renewal. Clonal cultures derived from single founder cells genera te neurons, astrocytes, and oligodendrocytes, confirming the multipotent na ture of the parent cell. Subcloning analysis showed that after serial passa ging, recloning, and expansion, these cells retained multipotentiality, ind icating that they are self-renewing. Transplantation of an in vitro-expande d clonal population of cells into the adult rat spinal cord resulted in the ir differentiation into glial cells only. However, after heterotopic transp lantation into the hippocampus, transplanted cells that integrated in the g ranular cell layer differentiated into cells characteristic of this region, whereas engraftment into other hippocampal regions resulted in the differe ntiation of cells with astroglial and oligodendroglial phenotypes. The data indicate that clonally expanded, multipotent adult progenitor cells from a non-neurogenic region are not lineage-restricted to their developmental or igin but can generate region-specific neurons in vivo when exposed to the a ppropriate environmental cues.