Induction of endogenous neural precursors in mouse models of spinal cord injury and disease

Abstract

Adult neural precursor cells (NPCs) in the mammalian central nervous system (CNS) have been demonstrated to be responsive to conditions of injury and disease. Here we investigated the response of NPCs in mouse models of spinal cord disease [motor neuron disease (MND)] with and without sciatic nerve axotomy, and spinal cord injury (SCI). We found that neither axotomy, nor MND alone brought about a response by Nestin-positive NPCs. However, the combination of the two resulted in mobilization of NPCs in the spinal cord. We also found that there was an increase in the number of NPCs following SCI which was further enhanced by systemic administration of the neuregulatory cytokine, leukaemia inhibitory factor (LIF). NPCs were demonstrated to differentiate into astrocytes in axotomized MND mice. However, significant differentiation into the various neural cell phenotypes was not demonstrated at 1 or 2 weeks following SCI. These data suggest that factors inherent to injury mechanisms are required for induction of an NPC response in the mammalian spinal cord.

Neuronal repair and replacement in spinal cord injury

“…However newly born cells in the spinal cord mainly exhibited markers of immature glial cells after differentiation and no consistent evidence of neurogenesis could be found [55]. Several studies report spontaneous progenitor cell division after spinal cord injury in mice [18,56], rats [57] and the rhesus monkey [20]. Liu and colleagues [18], for example, used transgenic mice expressing the LacZ reporter under the control of a nestin enhancer (promoter), to reveal an increase in neural progenitor cell (NPC) proliferation in the ependymal zone (EZ) of the central canal in the adult spinal cord after traumatic compression SCI.…”

Breeding status affects motoneuron number and muscle size in naked mole‐rats: Recruitment of perineal motoneurons?

“…The generation of spinal motoneurons, including perineal motoneur- ons, is normally complete during embryonic development (Breedlove et al, 1983;Altman and Bayer, 1984), and we are not aware of any demonstration of adult motoneurogenesis in a mammal. Neural progenitor cells reside in the gray matter of the spinal cord of adult mice and rats (Namiki and Tator, 1999;Horner et al, 2000;Yamamoto et al, 2001;Azari et al, 2005;Chi et al, 2006). These cells may proliferate and migrate in response to neural injury or disease, but, to date, there is no evidence that newly generated cells differentiate into motoneurons.…”

Enrichment of rat oligodendrocyte progenitor cells by magnetic cell sorting

“…Due to the pathological events and limited ability of the spinal cord to repair itself, therapeutic approaches are generally focused either on stimulation of endogenous oligodendoglial progenitors (Azari et al, 2005;Fawcett, 2006;Yang et al, 2006) pro-oligodendroglial cells for further transplantation application (Faulkner and Keirstead, 2005;Hofstetter et al, 2005;Ogawa et al, 2002;Teng et al, 2002).…”