title: The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor.
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 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.
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Suely Maymone
authors.initials: SM
authors.lastname: de Melo
authors.affiliation: Department of Physiology of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Bittencourt
authors.affiliation: Department of Physiology of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Enéas Galdini
authors.initials: EG
authors.lastname: Ferrazoli
authors.affiliation: Department of Physiology of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Clivandir Severino
authors.initials: CS
authors.lastname: da Silva
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Flavia Franco
authors.initials: FF
authors.lastname: da Cunha
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Flavia Helena
authors.initials: FH
authors.lastname: da Silva
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Roberta Sessa
authors.initials: RS
authors.lastname: Stilhano
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Priscila Martins Andrade
authors.initials: PM
authors.lastname: Denapoli
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Bianca Ferrarini
authors.initials: BF
authors.lastname: Zanetti
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Priscila Keiko Matsumoto
authors.initials: PK
authors.lastname: Martin
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Leonardo Martins
authors.initials: LM
authors.lastname: Silva
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Adara Aurea
authors.initials: AA
authors.lastname: dos Santos
authors.affiliation: Numpex-Bio, Nucleus of Multidisciplinary Research in Biology of the Universidade Federal do Rio de Janeiro-Xerém, São Paulo, Brazil.
authors.forename: Leandra Santos
authors.initials: LS
authors.lastname: Baptista
authors.affiliation: Department of Physiology of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Beatriz Monteiro
authors.initials: BM
authors.lastname: Longo
authors.affiliation: Research Center for Gene Therapy (CINTERGEN) of the Universidade Federal de São Paulo, São Paulo, Brazil; Department of Biophysics of the Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Han
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D024201:Bystander Effect / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000235:genetics; D014161:Transduction, Genetic; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014764:Viral Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir