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

• DOI: 10.1371/journal.pone.0128922
• Publication Date: 2015-06-12T21:53:23Z
• Authors: Suely Maymone de ...; Simone Bittencourt; Enéas Galdini Fer...; Clivandir Severin...; Flavia Franco da ...; Flavia Helena da ...; Roberta Sessa Sti...; Priscila Martins ...; Bianca Ferrarini ...; Priscila Keiko Ma...; Leonardo Martins ...; Adara Aurea dos S...; Leandra Santos Ba...; Beatriz Monteiro ...; Sang Won Han
• Keywords: 0301 basic medicine; Science; Q; R; Mice, Nude; Mesenchymal Stem Cells; Bystander Effect; Thymidine Kinase; Mice; Viral Proteins; 03 medical and health sciences; Adipose Tissue; Transduction, Genetic; Cell Line, Tumor; Medicine; Animals; Humans; Simplexvirus; Female; Glioblastoma; Ganciclovir; Research Article

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 μM ganciclovir (GCV). U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm2 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 mm2. 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.