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Volume 16, Number 23, Issue of December 1, 1996 pp. 7599-7609
Copyright ©1996 Society for Neuroscience

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

Received May 10, 1996; revised Aug. 16, 1996; accepted Sept. 10, 1996.

Samuel Weiss1, Christine Dunne1, Jennifer Hewson1, Cheryl Wohl1, Matt Wheatley1, Alan C. Peterson2, and Brent A. Reynolds1

1 Neuroscience Research Group, Departments of Anatomy and Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1, and 2 Division of Experimental Medicine and Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Molecular Oncology Group, H5-35, Royal Victoria Hospital, Montreal, Quebec, Canada H3A 1A1

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.

Key words: stem cells; spinal cord; ventricles; renewal; multipotent; epidermal growth factor; basic fibroblast growth factor




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