Gene therapy of experimental brain tumors using neural progenitor cells

Citation
S. Benedetti et al., Gene therapy of experimental brain tumors using neural progenitor cells, NAT MED, 6(4), 2000, pp. 447-450
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
NATURE MEDICINE
ISSN journal
1078-8956 → ACNP
Volume
6
Issue
4
Year of publication
2000
Pages
447 - 450
Database
ISI
SICI code
1078-8956(200004)6:4<447:GTOEBT>2.0.ZU;2-0
Abstract
Glioblastomas, the most frequent and malignant of primary brain tumors, hav e a very poor prognosis'. Gene therapy of glioblastomas is limited by the s hort survival of viral vectors and by their difficulty in reaching glioblas toma cells infiltrating the brain parenchyma. Neural stem/progenitor cells can be engineered to produce therapeutic molecules and have the potential t o overcome these limitations because they may travel along the white matter , like neoplastic cells, and engraft stably into the brain(2,3). Retrovirus -mediated transfer of the gene for interleukin-4 is an effective treatment for rat brain glioblastomas(4). Here, we transferred the gene for interleuk in-4 into C57BL6J mouse primary neural progenitor cells and injected those cells into established syngeneic brain glioblastomas. This led to the survi val of most tumor-bearing mice. We obtained similar results by implanting i mmortalized neural progenitor cells derived from Sprague-Dawley rats into C 6 glioblastomas. We also documented by magnetic resonance imaging the progr essive disappearance of large tumors, and detected 5-bromodeoxyuridine-labe led progenitor cells several weeks after the injection. These findings supp ort a new approach for gene therapy of brain tumors, based on the grafting of neural stem cells producing therapeutic molecules.