Isolation of multipotent neural precursors residing in the cortex of the adult human brain

Multipotent precursors able to generate neurons, astrocytes, and oligodendr ocytes have previously been isolated from human brain embryos and recently from neurogenic regions of the adult human brains. The isolation of multipo tent neural precursors from adult human should open new perspectives to stu dy adult neurogenesis and for brain repair. The present study describes the in vitro isolation from adult human brains of a progenitor responsive to b oth epidermal and basic fibroblast growth factors that forms spheres as it proliferates. Single spheres derived from various regions of the brain gene rate in vitro neurons, astrocytes, and oligodendrocytes. The clonal origin of the spheres was revealed by genomic viral insertion using lentiviral vec tor. Interestingly, this vector appears to be a potent tool for gene transf er into human neural progeny. Ninety-six percent of the spheres investigate d were multipotent. Multipotent precursors were isolated from all brain reg ions studied, including the temporal and the frontal cortex, the amygdala, the hippocampus, and the ventricular zone. This study is the first evidence that primitive precursors such as multipotent precursors exist in the adul t human cortex and can reside far from the ventricles. Neurogenesis derived from adult human progenitors differ to murine neurogenesis by the requirem ent of laminin for oligodendrocyte generation and by the action of basic-fi broblast growth factor and platelet derived growth factor that prevented th e formation of oligodendrocytes and neurons. Moreover, the differentiation of human adult precursors seems to differ from fetal ones: adult precursors do not necessitate the removal of mitogen for differentiation. These resul ts indicate that the study of adult multipotent precursors is a new platfor m to study adult human neurogenesis, potentially generate neural cells for transplantation, and design protocols for in vivo stimulation. (C) 2001 Aca demic Press.