title: Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment.
abstract: The purpose of this study was to investigate whether the secretome of human adipose-derived stem cells (hADSC) affects human glioblastoma (GBM) cancer stem cell (CSC) subpopulation or has any influence on drug resistance and cell migration, evaluating the safety of hADSCs for novel cancer therapies.
  
  
  
  hADSCs were maintained in contact with fresh culture medium to produce hADSCs conditioned medium (CM). GBM U87 cells were cultured with CM and sphere formation, expression of genes related to resistance and CSCs-MGMT, OCT4, SOX2, NOTCH1, MSI1-and protein expression of OCT4 and Nanog were analyzed. The influence of hADSC CM on GBM resistance to temozolomide (TMZ) was evaluated by measuring cumulative population doubling and hADSC CM influence on tumor cell migration was analyzed using transwell assay.
  
  
  
  hADSC CM did not alter CSC-related features such as sphere-forming capacity and expression of genes related to CSC. hADSC CM treatment alone did not change proliferation rate of U87 cells and, most important, did not alter the response of tumor cells to TMZ. However, hADSC CM secretome increased the migration capacity of glioblastoma cells.
  
  
  
  hADSC CM neither induced an enrichment of CSCs in U87 cells population nor interfered in the response to TMZ in culture. Nevertheless, paracrine factors released by hADSCs were able to modulate glioblastoma cells migration. These findings provide novel information regarding the safety of using hADSCs against cancer and highlight the importance of considering hADSC-tumor cells interactions in tumor microenvironment in the design of novel cell therapies.
authors.affiliation: Laboratory of Cell Biology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil; Department of Biophysics and Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Giovana Ravizzoni
authors.initials: GR
authors.lastname: Onzi
authors.affiliation: Department of Biophysics and Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Pítia Flores
authors.initials: PF
authors.lastname: Ledur
authors.affiliation: Laboratory of Cell Biology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Luana Dimer
authors.initials: LD
authors.lastname: Hainzenreder
authors.affiliation: Laboratory of Cell Biology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Ana Paula Santin
authors.initials: AP
authors.lastname: Bertoni
authors.affiliation: Department of Biophysics and Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Andrew Oliveira
authors.initials: AO
authors.lastname: Silva
authors.affiliation: Department of Biophysics and Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.affiliation: Laboratory of Cell Biology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil. Electronic address: marciawink@yahoo.com.br.
authors.forename: Márcia Rosângela
authors.initials: MR
authors.lastname: Wink
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000473:pathology; D020543:Proteome / Q000627:therapeutic use*; D018874:Spheroids, Cellular / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned; D020543:Proteome
keywords: cancer stem cell; conditioned medium; drug resistance; glioblastoma; mesenchymal stromal cell; migration