Brain tumor stem cells: identification and concepts.

The study of human brain tumors has characteristically emphasized the molecular and cellular analysis of the bulk tumor. There is increasing evidence in brain tumors and other malignancies that the tumor clone is functionally heterogeneous, however, existing in a cellular hierarchy based on small subpopulations of stem cells. These concepts were first definitively demonstrated in human acute myelogenous leukemia, in which regeneration of a diversely heterogeneous human leukemia cell population in a xenograft mouse model occurred only after injection of a rare relatively homogeneous population of leukemic cells that expressed hematopoietic stem cell markers. Recently, through advances in understanding of normal neural stem cell biology, the use of techniques for cell purification by flow cytometry, and the development of cell functional assays in vivo, the time was made ripe for several groups to characterize brain tumor stem cells (BTSCs). The BTSC resides in the cell fraction expressing the neural precursor cell surface marker CD133.