6533b823fe1ef96bd127f7ff

RESEARCH PRODUCT

Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy

Natale BelluardoSimonetta SipioneDaniele Filippo CondorelliElena CattaneoGiuseppa MudòVincenza Barresi

subject

Cancer ResearchPathologymedicine.medical_specialtyGenetic enhancementBrain tumorFlucytosineBiologyTransfectionCytosine DeaminaseRats Sprague-DawleyGliomamedicineEscherichia coliAnimalsProdrugsProgenitor cellMolecular BiologyCells CulturedNeuronsBrain NeoplasmsStem CellsCytosine deaminaseTransfectionGenetic TherapyGliomamedicine.diseaseNeural stem cellRatsTransplantationMolecular MedicineFluorouracilStem Cell Transplantation

description

Since neural progenitor cells can engraft stably into brain tumors and differentiate along the neuronal and glial line, we tested the hypothesis that transplanted cytosine deaminase (CD)-expressing ST14A cells (an immortalized neural progenitor cell line) can convert locally 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU) and produce a regression of glioma tumors. ST14A, retrovirally transduced with the E. coli CD gene, showed a strong bystander effect on glioma cells as assessed by in vitro assay. Intracerebral injection of C6 glioma cells generated a rapidly growing tumoral mass. DiI prelabeled ST14A, coinjected into the rat brain with C6 glioma cells, survived in the tumoral mass up to 10 days and their number was not affected by in vivo 5-FC treatment. In contrast, a significant decrease of the glioma tumoral mass (-50%) was observed in 5-FC-treated rats. 5-FC had no effect on the tumor in the absence of CD-expressing ST14A cells. Our results support the feasibility of systems based on intratumoral transplantation of prodrug-converting cells for brain tumor therapy.

10.1038/sj.cgt.7700580http://hdl.handle.net/20.500.11769/49062