Induced pluripotent stem cells without c-myc reduce airway responsiveness and allergic reaction in sensitized mice

Chien Ying Wang, Guang-Yuh Chiou, Yueh Chien, Chia Chao Wu, Tzee Chung Wu, Wen Tsung Lo, Shyi Jou Chen, Shih Hwa Chiou, Ho Jen Peng, Ching Feng Huang*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)958-965
Number of pages8
JournalTransplantation
Volume96
Issue number11
DOIs
StatePublished - 15 Dec 2013

Keywords

  • Airway hyperresponsiveness
  • Allergy
  • Asthma
  • c-Myc
  • Induced pluripotent stem cells

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    Wang, C. Y., Chiou, G-Y., Chien, Y., Wu, C. C., Wu, T. C., Lo, W. T., Chen, S. J., Chiou, S. H., Peng, H. J., & Huang, C. F. (2013). Induced pluripotent stem cells without c-myc reduce airway responsiveness and allergic reaction in sensitized mice. Transplantation, 96(11), 958-965. https://doi.org/10.1097/TP.0b013e3182a53ef7