Human adipose tissue-derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastoma

0376021 - ÚMCH 2013 RIV DE eng J - Journal Article
Altanerova, V. - Cihova, M. - Babič, Michal - Rychly, B. - Ondicova, K. - Mravec, B. - Altaner, C.
Human adipose tissue-derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastoma.
International Journal of Cancer. Roč. 130, č. 10 (2012), s. 2455-2463. ISSN 0020-7136. E-ISSN 1097-0215
Institutional research plan: CEZ:AV0Z40500505
Keywords : glioblastoma * mesenchymal stem cells * suicide gene therapy
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 6.198, year: 2012

Human adipose tissue-derived MSCs to express the suicide gene cytosine deaminase::uracil phosphoribosyltransferase to treat intracranial rat C6 glioblastoma was tested. Experiments simulated conditions of future clinical application for high-grade glioblastoma therapy by direct injections of therapeutic stem cells into tumor. Genetically modified therapeutic stem cells showed the tumor tropism when injected to a distant intracranial site and effectively inhibited glioblastoma growth after 5-fluorocytosine (5-FC) therapy. Coadministration of C6 cells and therapeutic stem cells with delayed 5-FC therapy improved the survival in a therapeutic stem cell dose-dependent manner and induced complete tumor regression. Continuous intracerebroventricular delivery of 5-FC using osmotic pump reduced the dose of prodrug required for the same therapeutic effect, and along with repeated administration of therapeutic stem cells increased the survival time without any detectable adverse effects.
Permanent Link: http://hdl.handle.net/11104/0208534