The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor

Author(s):Show less -

de Melo, Suely Maymone ^[1] ; Bittencourt, Simone ^[2] ; Ferrazoli, Eneas Galdini ^[2] ; da Silva, Clivandir Severino ^[2] ; da Cunha, Flavia Franco ^[1] ; da Silva, Flavia Helena ^[1] ; Stilhano, Roberta Sessa ^[1] ; Andrade Denapoli, Priscila Martins ^[1] ; Zanetti, Bianca Ferrarini ^[1] ; Matsumoto Martin, Priscila Keiko ^[1] ; Silva, Leonardo Martins ^[1] ; dos Santos, Adara Aurea ^[1] ; Baptista, Leandra Santos ^[3] ; Longo, Beatriz Monteiro ^[2] ; Han, Sang Won ^{[4, 1]}

Affiliation

^[1] Univ Fed Sao Paulo, Res Ctr Gene Therapy CINTERGEN, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Physiol, Sao Paulo - Brazil

^[3] Univ Fed Rio de Janeiro Xerem, Nucleus Multidisciplinary Res Biol, Numpex Bio, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 10, n. 6 JUN 12 2015.
• Web of Science Citations: 26

Abstract

Glioblastoma (GBM) is an infiltrative tumor that is difficult to eradicate. Treating GBM with mesenchymal stem cells (MSCs) that have been modified with the HSV-Tk suicide gene has brought significant advances mainly because MSCs are chemoattracted to GBM and kill tumor cells via a bystander effect. To use this strategy, abundantly present adipose-tissue-derived mesenchymal stem cells (AT-MSCs) were evaluated for the treatment of GBM in mice. AT-MSCs were prepared using a mechanical protocol to avoid contamination with animal protein and transduced with HSV-Tk via a lentiviral vector. The U-87 glioblastoma cells cultured with AT-MSC-HSV-Tk died in the presence of 25 or 50 mu M ganciclovir (GCV). U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm(2) after 4 weeks, but the injection of AT-MSC-HSV-Tk cells one week after the U-87 injection, combined with GCV treatment, drastically reduced tumors to smaller than 0.5 mm(2). Immunohistochemical analysis of the tumors showed the presence of AT-MSC-HSV-Tk cells only within the tumor and its vicinity, but not in other areas of the brain, showing chemoattraction between them. The abundance of AT-MSCs and the easier to obtain them mechanically are strong advantages when compared to using MSCs from other tissues. (AU)

• FAPESP's process: 12/21861-1 - Development of DNA vaccine against tumors expressing CEA using scFv (Single Chain Fragment Variable) derived of the idiotypic antibody 6.C4
• Grantee: Sang Won Han
• Support Opportunities: Regular Research Grants