title: Induced pluripotent stem cell lines derived from human gingival fibroblasts and periodontal ligament fibroblasts.
abstract: OBJECTIVE
  Human induced pluripotent stem (iPS) cells, which have similar properties to human embryonic stem (hES) cells, have been generated from neonatal and adult human dermal fibroblasts by reprogramming. iPS cells have high pluripotency and differentiation potential, and may be a potential autologous stem cell source for future regenerative therapy.
  
  
  METHODS
  iPS cell lines from human gingival fibroblasts and, for the first time, from periodontal ligament fibroblasts, were generated by reprogramming using a retroviral transduction cocktail of OCT3/4, SOX2, KLF4 and c-MYC. iPS induction was investigated through expression of the embryonic stem cell markers SSEA4, OCT4, NANOG, GCTM-2, TG30 and TRA-1-60. Following in vitro differentiation, the expression of genes for differentiation markers for ectoderm (SOX1, PAX6), mesoderm [RUNX1, T(Brachyury)] and endoderm (GATA4, AFP) was assessed by real-time RT-PCR. The ability to form teratomas following implantation into mouse testes was assessed by histology.
  
  
  RESULTS
  Human gingival fibroblast- and periodontal ligament fibroblast-derived iPS cells showed similar characteristics to hES cells. Both sets of iPS cells displayed colony morphology comparable to that of hES cells and expressed the hES cell-associated cell-surface antigens, SSEA3, SSEA4, GCTM-2, TG30 (CD9) and Tra-1-60, and the hES cell marker genes, OCT4, NANOG and GDF3. These iPS cells showed differentiation potential to form embryoid bodies in vitro and expressed genes for endoderm, ectoderm and mesoderm. Teratoma formation following implantation into mouse testes was observed.
  
  
  CONCLUSIONS
  These results demonstrate that iPS cells can be successfully generated from adult human gingival and periodontal ligament fibroblasts.
authors: School of Dentistry, Colgate Australian Clinical Dental Research Centre, University of Adelaide, Adelaide, SA, Australia.
authors: N
authors: N
authors: Wada
authors: B
authors: B
authors: Wang
authors: N-H
authors: NH
authors: Lin
authors: A L
authors: AL
authors: Laslett
authors: S
authors: S
authors: Gronthos
authors: P M
authors: PM
authors: Bartold
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000032:analysis; D005136:Eye Proteins / Q000032:analysis; D005326:Fetal Proteins / Q000032:analysis; D005347:Fibroblasts / Q000502:physiology*; D050991:GATA4 Transcription Factor / Q000032:analysis; D016259:Genes, myc / Q000235:genetics; D005881:Gingiva / Q000166:cytology*; D006028:Glycosphingolipids / Q000032:analysis; D055451:Growth Differentiation Factor 3 / Q000032:analysis; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D051379:Mice; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis; D010513:Periodontal Ligament / Q000166:cytology*; D011509:Proteoglycans / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis; D055748:SOXB1 Transcription Factors / Q000032:analysis / Q000235:genetics; D055746:Stage-Specific Embryonic Antigens / Q000032:analysis; D020825:T-Box Domain Proteins / Q000032:analysis; D013724:Teratoma / Q000473:pathology; D013736:Testicular Neoplasms / Q000473:pathology; D014161:Transduction, Genetic; D000509:alpha-Fetoproteins / Q000032:analysis; D000098908:Brachyury Protein
chemical_list: D000954:Antigens, Surface; D050676:Core Binding Factor Alpha 2 Subunit; D005136:Eye Proteins; D005326:Fetal Proteins; D050991:GATA4 Transcription Factor; D006028:Glycosphingolipids; D055451:Growth Differentiation Factor 3; D018398:Homeodomain Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011509:Proteoglycans; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D055746:Stage-Specific Embryonic Antigens; D020825:T-Box Domain Proteins; D000509:alpha-Fetoproteins; D000098908:Brachyury Protein; C484170:GATA4 protein, human; C525974:GDF3 protein, human; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C486780:NANOG protein, human; C000605730:PAX6 protein, human; C494173:POU5F1 protein, human; C000605732:Pax6 protein, mouse; C493728:RUNX1 protein, human; C490906:SOX1 protein, human; C527782:SOX2 protein, human; C107064:TRA-1-60 antigen, human; C066584:stage-specific embryonic antigen-4