title: Transient overexpression of Pparγ2 and C/ebpα in mesenchymal stem cells induces brown adipose tissue formation.
abstract: BACKGROUND
  Brown adipose tissue plays a pivotal role in mammal metabolism and thermogenesis. It has a great therapeutic potential in several metabolic disorders such as obesity and diabetes. Mesenchymal stem cells (MSCs) are suitable candidates for brown adipose tissue formation de novo. Pparγ2 and C/ebpα are nucleic receptors known to mediate adipogenic differentiation. We hypothesized that overexpression of the Pparγ2 and C/ebpα genes in MSCs would lead to the formation of adipose tissue.
  
  
  METHODS
  MSCs bearing the Luc reporter gene were transfected to overexpress Pparγ2 and C/ebpα. Differentiation of nucleofected cells was evaluated in vitro and in vivo following ectopic implantation of the cells in C3H/HeN mice.
  
  
  RESULTS
  After implantation, the engineered cells survived for 5 weeks and brown adipose-like tissue was observed in histological samples. Immunostaining and bioluminescent imaging showed new adipocytes expressing Luc and the brown adipose tissue marker, UCP1, in vitro and in vivo.
  
  
  CONCLUSIONS
  We show that gene delivery of transcription factors into MSCs generates brown adipose tissue in vitro and in vivo.
authors.affiliation: Skeletal Biotech Laboratory, Hebrew University-Hadassah, Faculty of Dental Medicine, Jerusalem, Israel.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Sheyn
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.forename: Wafa
authors.initials: W
authors.lastname: Tawackoli
authors.forename: Susan
authors.initials: S
authors.lastname: Su
authors.forename: Shiran
authors.initials: S
authors.lastname: Ben-David
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D020869:Gene Expression Profiling; D005818:Genetic Engineering; D057809:HEK293 Cells; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008163:Luminescent Measurements; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D047495:PPAR gamma / Q000378:metabolism*; D014162:Transfection; D000071256:Uncoupling Protein 1
chemical_list: D015415:Biomarkers; D022763:CCAAT-Enhancer-Binding Protein-alpha; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1