Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas

One of the impediments to the treatment of brain tumors (e.g., gliomas) has been the degree to which they expand, infiltrate surrounding tissue, and m igrate widely into normal brain, usually rendering them "elusive" to effect ive resection, irradiation, chemotherapy, or gene therapy. We demonstrate t hat neural stem cells (NSCs), when implanted into experimental intracranial gliomas in vivo in adult rodents, distribute themselves quickly and extens ively throughout the tumor bed and migrate uniquely in juxtaposition to wid ely expanding and aggressively advancing tumor cells, while continuing to s tably express a foreign gene. The NSCs "surround" the invading tumor border while "chasing down" infiltrating tumor cells. When implanted intracranial ly at distant sites from the tumor (e.g., into normal tissue, into the cont ralateral hemisphere, or into the cerebral ventricles), the donor cells mig rate through normal tissue targeting the tumor cells (including human gliob lastomas). When implanted outside the CNS intravascularly. NSCs will target an intracranial tumor. NSCs can deliver a therapeutically relevant molecul e-cytosine deaminase-such that quantifiable reduction in tumor burden resul ts. These data suggest the adjunctive use of inherently migratory NSCs as a delivery vehicle for targeting therapeutic genes and vectors to refractory , migratory, invasive brain tumors. More broadly, they suggest that NSC mig ration can be extensive, even in the adult brain and along nonstereotypical routes, if pathology (as modeled here by tumor) is present.