Isolation of Multipotent Neural Precursors Residing in the Cortex of the Adult Human Brain

• Published in: Experimental neurology Vol. 170; no. 1; pp. 48 - 62
• Main Authors: Arsenijevic, Yvan, Villemure, Jean-Guy, Brunet, Jean-François, Bloch, Jocelyne J., Déglon, Nicole, Kostic, Corinne, Zurn, Anne, Aebischer, Patrick
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.07.2001; Elsevier
• Subjects: Adolescent; Adult; amygdala; Amygdala - cytology; Amygdala - drug effects; Antigens, Differentiation - biosynthesis; Biological and medical sciences; Brain - cytology; Brain - drug effects; Cell Differentiation; Cell Division - drug effects; Cell Separation; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Child; Child, Preschool; Clone Cells - cytology; Epidermal Growth Factor - pharmacology; Extrachromosomal Inheritance; Fibroblast Growth Factor 2 - pharmacology; Fundamental and applied biological sciences. Psychology; GFAP; gliogenesis; human brain; Humans; Infant; Isolated neuron and nerve. Neuroglia; lentivirus; Middle Aged; neurite branching; neurogenesis; Neuroglia - cytology; Neuroglia - metabolism; Neurons - cytology; Neurons - metabolism; oligodendrocytes; stem cells; Stem Cells - cytology; Stem Cells - drug effects; SVZ; Vertebrates: nervous system and sense organs; stem cells; gliogenesis; amygdala; human brain; SVZ; neurogenesis; oligodendrocytes; neurite branching; lentivirus; GFAP; Human; Amygdala; Central nervous system; Precursor cell; Temporal cortex; Basic fibroblast growth factor; Astrocyte; Frontal cortex; Cell differentiation; Primitive; Epidermal growth factor; Laminin; Neuron; Oligodendrocyte; Transfer; Adult; Isolation; Hippocampus; Brain (vertebrata)
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2001.7691

Multipotent precursors able to generate neurons, astrocytes, and oligodendrocytes have previously been isolated from human brain embryos and recently from neurogenic regions of the adult human brains. The isolation of multipotent neural precursors from adult human should open new perspectives to study adult neurogenesis and for brain repair. The present study describes the in vitro isolation from adult human brains of a progenitor responsive to both epidermal and basic fibroblast growth factors that forms spheres as it proliferates. Single spheres derived from various regions of the brain generate in vitro neurons, astrocytes, and oligodendrocytes.The clonal origin of the spheres was revealed by genomic viral insertion using lentiviral vector. Interestingly, this vector appears to be a potent tool for gene transfer into human neural progeny. Ninety-six percent of the spheres investigated were multipotent. Multipotent precursors were isolated from all brain regions 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 adulthuman cortex and can reside far from the ventricles.Neurogenesis derived from adult humanprogenitors differ to murine neurogenesis by therequirement of laminin for oligodendrocyte generation and by the action of basic-fibroblast growth factor and platelet derived growth factor that prevented the 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 results indicate that the study of adult multipotent precursors is a new platform to study adult human neurogenesis, potentially generate neural cells for transplantation, and design protocols for in vivo stimulation.