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Intravascular delivery of neural stem cell lines
to target intracranial and extracranial tumors of neural and non-neural origin
Brown AB, Yang W, Schmidt NO, Carroll R, Leishear KK, Rainov NG, Black PM,
Breakefield XO, Aboody KS
Molecular Neurogenetics Unit, Department of Neurology,
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
The remarkable migratory and tumor-tropic capacities of neural stem cells (NSCs
and/or neuroprogenitor cells) represent a potentially powerful approach to the
treatment of invasive brain tumors, such as malignant gliomas.
We have previously shown that whether implanted directly into or at distant
sites from an experimental intracranial glioma, NSCs distributed efficiently
throughout the main tumor mass and also tracked advancing tumor cells, while
stably expressing a reporter transgene.
As therapeutic proof-of-concept, NSCs genetically modified to produce the
prodrug activating enzyme cytosine deaminase (CD), effected an 80% reduction in
the resultant tumor mass, when tumor animals were treated with the systemic
prodrug, 5-fluorocytosine.
We now extend our findings of the tumor-tropic properties of NSCs (using a
well-characterized, clonal NSC line C17.2), by investigating their capacity to
target both intracranial and extracranial tumors, when administered into the
peripheral vasculature.
We furthermore demonstrate their capacity to target extracranial non-neural
tumors such as prostate cancer and malignant melanoma.
Well-characterized NSC lines (lacZ and/or CD-positive) were injected into the
tail vein of adult nude mice with established experimental intracranial and/or
subcutaneous flank tumors of neural and non-neural origin.
The time course and distribution of NSCs within the tumor and internal organs
was assessed in various models.
Resulting data suggest that NSCs can localize to various tumor sites when
injected via the peripheral vasculature, with little accumulation in normal
tissues.
Our findings suggest the novel use of intravascularly administered NSCs as an
effective delivery vehicle to target and disseminate therapeutic agents to
invasive tumors of neural and nonneural origin, both within and outside of the
brain.
PMID: 14670128 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14670128
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