C J Chiu1, T Y Ling, B L Chiang. 1. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Abstract
BACKGROUND: Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness (AHR). Little is known about the role of pulmonary stem/progenitor cells (PSCs) in allergic airway inflammation. METHODS: To identify and investigate the role of PSCs in the bronchial epithelium of neonatal mice, we developed an enzyme-based digestion method to obtain single-cell suspension from lung tissues. Characterization of PSCs was performed using flow cytometry, real-time PCR, immunofluorescence staining, confocal microscopy, and scanning electron microscopy. The effects of SSEA-1(+) (stage-specific embryonic antigen-1) PSCs was studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of cell-based regulation using flow cytometry, real-time PCR, and immune-blotting. RESULTS: Single-cell suspensions derived from neonatal lung tissue included populations that expressed either SSEA-1(+) or Sca-1(+) (stem cell antigen-1). The SSEA-1(+) PSCs were highly prevalent in neonatal mice, and they were rare in adult mice. Enriched neonatal SSEA-1(+) PSCs had the ability of self-renewal and differentiated into pneumocytes and tracheal epithelial cells. SSEA-1(+) PSCs reduced AHR and airway damage in asthmatic mice by decreasing eosinophil infiltration, inhibiting chemokines/cytokines production, and preserving the level of CCSP. CONCLUSIONS: Here, we demonstrated that neonatal SSEA-1(+) PSCs play an immunomodulatory role in the progression of asthma by reducing lung damage and inhibiting inflammatory responses. Further understanding the molecular mechanisms of neonatal SSEA-1(+) PSCs might shed light on exploring the novel therapeutic approaches for allergic airway inflammation.
BACKGROUND:Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness (AHR). Little is known about the role of pulmonary stem/progenitor cells (PSCs) in allergic airway inflammation. METHODS: To identify and investigate the role of PSCs in the bronchial epithelium of neonatal mice, we developed an enzyme-based digestion method to obtain single-cell suspension from lung tissues. Characterization of PSCs was performed using flow cytometry, real-time PCR, immunofluorescence staining, confocal microscopy, and scanning electron microscopy. The effects of SSEA-1(+) (stage-specific embryonic antigen-1) PSCs was studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of cell-based regulation using flow cytometry, real-time PCR, and immune-blotting. RESULTS: Single-cell suspensions derived from neonatal lung tissue included populations that expressed either SSEA-1(+) or Sca-1(+) (stem cell antigen-1). The SSEA-1(+) PSCs were highly prevalent in neonatal mice, and they were rare in adult mice. Enriched neonatal SSEA-1(+) PSCs had the ability of self-renewal and differentiated into pneumocytes and tracheal epithelial cells. SSEA-1(+) PSCs reduced AHR and airway damage in asthmatic mice by decreasing eosinophil infiltration, inhibiting chemokines/cytokines production, and preserving the level of CCSP. CONCLUSIONS: Here, we demonstrated that neonatal SSEA-1(+) PSCs play an immunomodulatory role in the progression of asthma by reducing lung damage and inhibiting inflammatory responses. Further understanding the molecular mechanisms of neonatal SSEA-1(+) PSCs might shed light on exploring the novel therapeutic approaches for allergic airway inflammation.
Authors: Soraia C Abreu; Mariana A Antunes; Debora G Xisto; Fernanda F Cruz; Vivian C Branco; Elga Bandeira; Jamil Zola Kitoko; Almair F de Araújo; Ludmilla Dellatorre-Texeira; Priscilla C Olsen; Daniel J Weiss; Bruno L Diaz; Marcelo M Morales; Patricia R M Rocco Journal: Stem Cells Transl Med Date: 2017-04-20 Impact factor: 6.940