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Transplantation of human neural progenitor cells into the neonatal rat brain: extensive migration and differentiation with long-distance axonal projections.

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Author

Summary, in English

Here we examined the ability of human neural progenitors from the embryonic forebrain, expanded for up to a year in culture in the presence of growth factors, to respond to environmental signals provided by the developing rat brain. After survival times of up to more than a year after transplantation into the striatum, the hippocampus, and the subventricular zone, the cells were analyzed using human-specific antisera and the reporter gene green fluorescent protein (GFP). From grafts implanted in the striatum, the cells migrated extensively, especially within white matter structures. Neuronal differentiation was most pronounced at the striatal graft core, with axonal projections extending caudally along the internal capsule into mesencephalon. In the hippocampus, cells migrated throughout the entire hippocampal formation and into adjacent white matter tracts, with differentiation into neurons both in the dentate gyrus and in the CA1-3 regions. Directed migration along the rostral migratory stream to the olfactory bulb and differentiation into granule cells were observed after implantation into the subventricular zone. Glial differentiation occurred at all three graft sites, predominantly at the injection sites, but also among the migrating cells. A lentiviral vector was used to transduce the cells with the GFP gene prior to grafting. The reporter gene was expressed for at least 15 weeks and the distribution of the gene product throughout the entire cytoplasmic compartment of the expressing cells allowed for a detailed morphological analysis of a portion of the grafted cells. The extensive integration and differentiation of in vitro-expanded human neural progenitor cells indicate that multipotent progenitors are capable of responding in a regionally specific manner to cues present in the developing rat brain.

Publishing year

2002

Language

English

Pages

1-21

Publication/Series

Experimental Neurology

Volume

173

Issue

1

Document type

Journal article

Publisher

Elsevier

Topic

  • Neurology

Keywords

  • Brain Tissue Transplantation
  • Axons : ultrastructure
  • Animal
  • Animals Newborn
  • Human
  • Hippocampus : cytology : metabolism
  • Lateral Ventricles : cytology : metabolism
  • Luminescent Proteins : biosynthesis : genetics
  • Prosencephalon : cytology : embryology : transplantation
  • Neurons : cytology : metabolism : ultrastructure
  • Neuroglia : cytology : metabolism : ultrastructure
  • Rats
  • Rats Sprague-Dawley
  • Support Non-U.S. Gov't
  • Stem Cells : cytology : metabolism : transplantation
  • Cell Count
  • Cell Differentiation : physiology
  • Cell Line
  • Cell Movement : physiology
  • Corpus Striatum : cytology : metabolism
  • Fetal Tissue Transplantation
  • Genes Reporter
  • Graft Survival

Status

Published

Research group

  • CNS Gene Therapy
  • Neurobiology

ISBN/ISSN/Other

  • ISSN: 0014-4886