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Transplantation of
prodrug-converting neural progenitor cells for brain tumor therapy
Vincenza Barresi, Natale Belluardo,
Simonetta Sipione, Giuseppa Mudò, Elena Cattaneo and Daniele Filippo Condorelli
Department of Chemical Sciences,
Section of Biochemistry and Molecular Biology, University of Catania, Italy
[V.B., D.F.P.]; Department of Experimental Medicine, University of Palermo,
Italy [N.B., G.M.]; Department of Pharmacological Sciences, University of Milan,
Italy [S.S., E.C.].
Correspondence to: Professor DF Condorelli, Sezione di Biochimica e Biologia
Molecolare, Dipartimento di Scienze Chimiche, Facoltà di Medicina, Università
di Catania, Viale A. Doria, 6, 95125 Catania, Italy. E-mail:
condorda@mbox.unict.it.
Received 22 November 2002
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.
Keywords: gene therapy; cytosine
deaminase; glioma; neural progenitor cells
© 2003 Nature Publishing Group
Source: http://www.nature.com/cgi-taf/DynaPage.taf?file=/cgt/journal/v10/n5/abs/7700580a.html&dynoptions=doi1092205197
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