Adult Spinal Cord Stem Cells Generate Neurons after Transplantation in the Adult Dentate Gyrus

By L. Shihabuddin, P. Horner, J. Ray, Fred H. Gage. 2000

738 citations recorded by the source corpus.

The adult rat spinal cord contains cells that can proliferate and differentiate into astrocytes and oligodendroglia in situ. Using clonal and subclonal analyses we demonstrate that, in contrast to progenitors isolated from the adult mouse spinal cord with a combination of growth factors, progenitors isolated from the adult rat spinal cord using basic fibroblast growth factor alone display stem cell properties as defined by their multipotentiality and self-renewal. Clonal cultures derived from single founder cells generate neurons, astrocytes, and oligodendrocytes, confirming the multipotent nature of the parent cell. Subcloning analysis showed that after serial passaging, recloning, and expansion, these cells retained multipotentiality, indicating that they are self-renewing. Transplantation of an in vitro-expanded clonal population of cells into the adult rat spinal cord resulted in their differentiation into glial cells only. However, after heterotopic transplantation into the hippocampus, transplanted cells that integrated in the granular cell layer differentiated into cells characteristic of this region, whereas engraftment into other hippocampal regions resulted in the differentiation 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 origin but can generate region-specific neurons in vivowhen exposed to the appropriate environmental cues.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Genetics

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Developmental Neuroscience

In Genetics

Citations in the corpus

Adult neurogenesis in brain repair: cellular plasticity vs. cellular replacement (2014, background): “The therapeutic potential of the transplanted stem cells have been validated in various models of diseases and injuries (Shihabuddin et al., 2000; Pluchino et al., 2003; Cummings et al., 2005; Jin et al., 2005).”
Neurogenesis in the Adult Hippocampus. (2015, background): “However, when transplanted into an area that is permissive for neuronal development, such as the dentate gyrus, their potential can be utilized (Suhonen et al. 1996; Shihabuddin et al. 2000).”
Neurogenesis in the Adult Brain (2002, background): “…and Weiss, 1992; Richards et al., 1992) and then in the dentate gyrus of the hippocampus (Gage et al., 1995; Palmer et al., 1997), and in most structures of the brain examined (Palmer et al., 1995; Shihabuddin et al., 2000), even where no neurons existed (Palmer et al., 1999; Kondo and Raff, 2000).”
The development of neural stem cells (2001, background): “For example, adult spinal-cord-derived stem cells, which do not normally make neurons, can make interneurons if injected into the adult hippocampu”
Neurogenesis in the adult brain: new strategies for central nervous system diseases. (2004, background): “, nonneurogenic) regions will differentiate into glial cells when transplanted back into the region of their origin, they will give rise to neurons when transplanted into the neurogenic hippocampus (17, 46).”
Excitation-neurogenesis coupling in adult neural stem/progenitor cells. (2004, neutral): “1996; Shihabuddin et al., 2000).”
Subventricular Zone-Derived Neuroblasts Migrate and Differentiate into Mature Neurons in the Post-Stroke Adult Striatum (2006, result): “2), and this finding is consistent with the idea that the distribution of the neurogenic cell population is restricted to a niche in which a special microenvironment supports their survival and function in the adult brain (Herrera et al., 1999; Shihabuddin et al., 2000).”
Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells (2006, background): “The population specificity of neuronal death was found to be essential, allowing maintenance of local circuitry and survival of surrounding cells that alter gene expression to direct precursors (Wang et al. 1998; Shin et al. 2000; Fricker-Gates et al. 2002).”
Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. (2003, background): “Previous studies have reported the feasibility of transplantation of neural stem cells or fetal spinal cord cells into intact or injured spinal cords and reported limited stem cell differentiation (Cao et al., 2001; Chow et al., 2000; Hammang et al., 1997; Liu et al., 1999; McDonald et al., 1999; On”
Mesenchymal stem cells: clinical applications and biological characterization. (2004, background): “Stem cells with the ability to differentiate into neurons, astrocytes and oligodendrocytes have been isolated from rat spinal cord ( Shihabuddin, Horner, Ray, & Gage, 2000 ), and implantation of neural stem cells in an adult rat model of spinal cord injury resulted in long-term functional improvemen”
The Adult Substantia Nigra Contains Progenitor Cells with Neurogenic Potential (2002, background): “The adult hippocampus has been demonstrated to provide signals that can direct multipotent cells from different CNS regions toward a neuronal fate (Suhonen et al., 1996; Shihabuddin et al., 2000).”