title: Induced pluripotent stem cells without c-Myc reduce airway responsiveness and allergic reaction in sensitized mice.
abstract: BACKGROUND
  Allergic disorders have increased substantially in recent years. Asthma is characterized by airway damage and remodeling. Reprogramming induced pluripotent stem cells (iPSCs) from adult somatic cells transfected by Oct-4/Sox-2/Klf-4, but not c-Myc, has shown the potential of embryonic-like cells. These cells have potential for multilineage differentiation and provide a resource for stem cell-based utility. However, the therapeutic potential of iPSCs without c-Myc (iPSC-w/o-c-Myc) in allergic diseases and airway hyperresponsiveness has not been investigated. The aim of this study was to evaluate the therapeutic effect of iPSC-w/o-c-Myc transplantation in a murine asthma model.
  
  
  METHODS
  BALB/c mice were sensitized with alum-adsorbed ovalbumin (OVA) and then challenged with aerosolized OVA. Phosphate-buffered saline or iPSC-w/o-c-Myc was then intravenously injected after inhalation. Serum allergen-specific antibody levels, airway hyperresponsiveness, cytokine levels in spleen cells and bronchoalveolar lavage fluid (BALF), and cellular distribution in BALF were then examined.
  
  
  RESULTS
  Treatment with iPSC-w/o-c-Myc effectively suppressed both Th1 and Th2 antibody responses, which was characterized by reduction in serum allergen-specific IgE, IgG, IgG1, and IgG2a levels as well as in interleukin-5 and interferon-γ levels in BALF and in OVA-incubated splenocytes. Meanwhile, regulatory cytokine, interleukin-10, was enhanced. Transplantation of iPSC-w/o-c-Myc also significantly attenuated cellular infiltration in BALF and allergic airway hyperresponsiveness. However, no tumor formation was observed 6 months after transplantation.
  
  
  CONCLUSIONS
  Administration of iPSC-w/o-c-Myc not only inhibited Th1 inflammatory responses but also had therapeutic effects on systemic allergic responses and airway hyperresponsiveness. iPSC-w/o-c-Myc transplantation may be a potential modality for treating allergic reactions and bronchial asthma.
authors.affiliation: 1 Department of Medical Research & Education, Taipei Veterans General Hospital, Taipei, Taiwan. 2 School of Medicine, National Yang-Ming University, Taipei, Taiwan. 3 Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan. 4 Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan. 5 Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 6 Address correspondence to: Ching-Feng Huang, M.D., Ph.D., Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Gong Road, Neihu District, Taipei 114, Taiwan.
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Wang
authors.forename: Guang-Yuh
authors.initials: GY
authors.lastname: Chiou
authors.forename: Yueh
authors.initials: Y
authors.lastname: Chien
authors.forename: Chia-Chao
authors.initials: CC
authors.lastname: Wu
authors.forename: Tzee-Chung
authors.initials: TC
authors.lastname: Wu
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Lo
authors.forename: Shyi-Jou
authors.initials: SJ
authors.lastname: Chen
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.forename: Ho-Jen
authors.initials: HJ
authors.lastname: Peng
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Huang
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D018836:Inflammation Mediators / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010047:Ovalbumin; D016271:Proto-Oncogene Proteins c-myc / Q000172:deficiency*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D014162:Transfection
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489428:Myc protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin