Segregation of Human Neural Stem Cells in the Developing Primate Forebrain

Abstract

Many central nervous system regions at all stages of life contain neural stem cells (NSCs). We explored how these disparate NSC pools might emerge. A traceable clone of human NSCs was implanted intraventricularly to allow its integration into cerebral germinal zones of Old World monkey fetuses. The NSCs distributed into two subpopulations: One contributed to corticogenesis by migrating along radial glia to temporally appropriate layers of the cortical plate and differentiating into lamina-appropriate neurons or glia; the other remained undifferentiated and contributed to a secondary germinal zone (the subventricular zone) with occasional members interspersed throughout brain parenchyma. An early neurogenetic program allocates the progeny of NSCs either immediately for organogenesis or to undifferentiated pools for later use in the "postdevelopmental" brain.

Noninvasive method of immortalized neural stem-like cell transplantation in an experimental model of Huntington's disease

“…In the case of genetically manipulated human NSC clones (v-myc+), however, the propagating gene product v-myc is undetectable in donor human cells after engraftment (Flax et al, 1998), despite the fact that the brains of transplant recipients contain numerous stably engrafted donor-derived cells. In addition, previous observations showed the invariant absence of brain tumors derived from implanted v-myc-propagated NSCs, even after several years in rodents (Snyder et al, 1992;Jeong et al, 2003;Chu et al, 2003Chu et al, , 2004a or in primates (Ourednik et al, 2001), which is consistent with the loss of v-myc expression from stably engrafted NSCs following transplantation. We also detected no tumorigenesis in the present study.…”

Intravenous administration of human neural stem cells induces functional recovery in Huntington's disease rat model

“…Primary dissociated cell cultures were prepared from embryonic human brains of 15 weeks gestation as described previously (Cho et al, 2002;Chu et al, 2004a,b;Jeong et al, 2003;Ourednik et al, 2001). To provide an unambiguous molecular tag for identifying the implanted cells, the cell line was infected with a replication-incompetent retroviral vector encoding b-galactosidase (b-gal; Lac z) and puromycin-resistant genes.…”

“…HB1.F3 cells grown on coverslips were immunoreaction positive for nestin, the cell type-specific marker of NSCs. Detailed cell line characteristics are described in previous reports (Cho et al, 2002;Chu et al, 2004a,b;Jeong et al, 2003;Ourednik et al, 2001). NSCs were preincubated in culture (at a density of 5 Â 10 5 cells/mL) with BrdU (10 mM, Sigma, USA) for 48 h before implantation in order to be subsequently identifiable in vivo by their BrdUimmunopositive nuclei, as previously described (Ourednik et al, 2001).…”

Bcl-XL modulates the differentiation of immortalized human neural stem cells

“…1,2,[23][24][25] Since neurodegenerative diseases are in many cases lateonset diseases, we found therefore of interest to study the in vivo properties of control or Bcl-X L overexpressing hNS1 cells after transplantation into the aged rat brain. Consistent with the in vitro data, we have also observed an increased neuron production and a diminished glia yield from Bcl-X L -overexpressing hNS1 cell transplants.…”