Multipotent CNS Stem Cells Are Present in the Adult Mammalian Spinal Cord and Ventricular Neuroaxis

Abstract

Neural stem cells in the lateral ventricles of the adult mouse CNS participate in repopulation of forebrain structures in vivo and are amenable to in vitro expansion by epidermal growth factor (EGF). There have been no reports of stem cells in more caudal brain regions or in the spinal cord of adult mammals. In this study we found that although ineffective alone, EGF and basic fibroblast growth factor (bFGF) cooperated to induce the proliferation, self-renewal, and expansion of neural stem cells isolated from the adult mouse thoracic spinal cord. The proliferating stem cells, in both primary culture and secondary expanded clones, formed spheres of undifferentiated cells that were induced to differentiate into neurons, astrocytes, and oligodendrocytes. Neural stem cells, whose proliferation was dependent on EGF+bFGF, were also isolated from the lumbar/sacral segment of the spinal cord as well as the third and fourth ventricles (but not adjacent brain parenchyma). Although all of the stem cells examined were similarly multipotent and expandable, quantitative analyses demonstrated that the lateral ventricles (EGF-dependent) and lumbar/sacral spinal cord (EGF+bFGF-dependent) yielded the greatest number of these cells. Thus, the spinal cord and the entire ventricular neuroaxis of the adult mammalian CNS contain multipotent stem cells, present at variable frequency and with unique in vitro activation requirements.

Dopaminergic modulation of neurogenesis in the subventricular zone of the adult brain

“…36 In 1996, Reynolds and Weiss isolated neurosphereforming cells from the adult lateral ventricle and spinal cord. 37 The latter precursors required the combined effect of FGF-2 and EGF in order to proliferate however; precursors isolated from the lateral ventricles were EGF-dependent. This EGF dependency could be due to the presence of C cells and their immediate precursors in this particular region, a situation that is not seen at other sites.…”

Mechanism of stem cells in the central nervous system

“…4) it was demonstrated that these labeled cells, in vitro, under clonal conditions, can generate neurospheres that harbor astrocytes, oligodendrocytes, and neurons. They appeared to be CNS stem cells (Clarke et al, 1994;Weiss et al, 1996;Johansson, 2002). But what about the ependymal cells in the brain?…”

Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction

“…In support of this viewpoint, coculture experiments have shown that ECs increase proliferation of NSPCs derived from the adult SVZ, thereby promoting neurogenesis [6,7]. However, accumulating evidence indicates that NSPCs are present in many parts of the adult brain, including the cortex [8][9][10], subcortical white matter [11], and spinal cord [12][13][14]; that is, outside conventional neurogenic zones, including SVZ and SGZ. Recently, we also found that NSPCs developed in the poststroke area of the cortex in the adult murine brain (ischemia-induced NSPCs) [8], and that ECs promoted the proliferation of these NSPCs, thereby enhancing neurogenesis after ischemia [15].…”