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1 Stem Cell Research Institute and 2 Laboratory of Molecular Diagnostics, H. S. Raffaele, Milan, Italy; 3 National Neurological Institute "C. Besta," Milan, Italy; 4 Department of Neurological Surgery, Johns Hopkins Medical School, Baltimore, Maryland; and 5 Department of Biological Sciences and Biotechnology, University of Milano-Bicocca, Milan, Italy
Transformed stem cells have been isolated from some human cancers. We report that, unlike other brain cancers, the lethal glioblastoma multiforme contains neural precursors endowed with all of the critical features expected from neural stem cells. Similar, yet not identical, to their normal neural stem cell counterpart, these precursors emerge as unipotent (astroglial) in vivo and multipotent (neuronal-astroglial-oligodendroglial) in culture. More importantly, these cells can act as tumor-founding cells down to the clonal level and can establish tumors that closely resemble the main histologic, cytologic, and architectural features of the human disease, even when challenged through serial transplantation. Thus, cells possessing all of the characteristics expected from tumor neural stem cells seem to be involved in the growth and recurrence of adult human glioblastomas multiforme.
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