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The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase.

Authors
Chang, DY; Yoo, SW; Hong, Y; Kim, S; Kim, SJ; Yoon, SH; Cho, KG; Paek, SH; Lee, YD; Kim, SS; Suh-Kim, H
Citation
International journal of cancer, 127(8):1975-1983, 2010
Journal Title
International journal of cancer
ISSN
0020-71361097-0215
Abstract
Suicide genes have recently emerged as an attractive alternative therapy for the treatment of various types of intractable cancers. The efficacy of suicide gene therapy relies on efficient gene delivery to target tissues and the localized concentration of final gene products. Here, we showed a potential ex vivo therapy that used mesenchymal stem cells (MSCs) as cellular vehicles to deliver a bacterial suicide gene, cytosine deaminase (CD) to brain tumors. MSCs were engineered to produce CD enzymes at various levels using different promoters. When co-cultured, CD-expressing MSCs had a bystander, anti-cancer effect on neighboring C6 glioma cells in proportion to the levels of CD enzymes that could convert a nontoxic prodrug, 5-fluorocytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) in vitro. Consistent with the in vitro results, for early stage brain tumors induced by intracranial inoculation of C6 cells, transplantation of CD-expressing MSCs reduced tumor mass in proportion to 5-FC dosages. However, for later stage, established tumors, a single treatment was insufficient, but only multiple transplantations were able to successfully repress tumor growth. Our findings indicate that the level of total CD enzyme activity is a critical parameter that is likely to affect the clinical efficacy for CD gene therapy. Our results also highlight the potential advantages of autograftable MSCs compared with other types of allogeneic stem cells for the treatment of recurrent glioblastomas through repetitive treatments.
MeSH terms
AdolescentAnimalsBrain Neoplasms/metabolismBrain Neoplasms/pathology*Brain Neoplasms/prevention & control*Bystander EffectChildChromatography, High Pressure LiquidCytosine Deaminase/metabolism*Flucytosine/metabolismFluorouracil/metabolismGene Therapy*HumansMaleMesenchymal Stem Cell Transplantation*Mesenchymal Stem Cells/enzymology*RatsRats, Sprague-DawleyTumor Cells, Cultured
DOI
10.1002/ijc.25383
PMID
20473873
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
Journal Papers > School of Medicine / Graduate School of Medicine > Urology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
AJOU Authors
장, 다영유, 승완김, 세중조, 경기이, 영돈김, 성수서, 해영
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