Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma

Ismail Ogulur; Gulben Gurhan; Faruk Erdem Kombak; Deniz Filinte; Isil Barlan; Tunc Akkoc

doi:10.1016/j.intimp.2014.06.011

Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma

Ismail Ogulur, Gulben Gurhan, Faruk Erdem Kombak, Deniz Filinte, Isil Barlan, Tunc Akkoc^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

New strategies are needed to suppress airway inflammation and prevent or reverse airway remodeling in asthma. Reprogramming induced pluripotent stem cells (iPSCs) have the potential of embryonic stem cells (ESCs) and provide a resource for stem cell-based utility. The aim of this study was to evaluate the histopathological and immunomodulatory effects of ESCs and iPSCs for potential allogenic application in a murine model of acute asthma. BALB/c mice were sensitized with alum-absorbed ovalbumin (OVA) and then challenged with 1% aerosolized OVA. 5 × 10⁵ ESCs and iPSCs were administrated intranasally on the last day of nebulization. Mice were sacrificed after 24 h, and serum allergen specific antibody level, airway remodeling, cytokine levels in lung supernatants, and eosinophilic infiltration in BAL fluid were examined. As a result, more ESCs and iPSCs integrated into the lungs of mice in OVA groups than those of the controls. Epithelial, smooth muscle and basal membrane thicknesses as well as goblet cell hyperplasia occurring in airway remodeling were significantly suppressed by pluripotent stem cells in both distal and proximal airways. Percentage of eosinophils decreased significantly in BAL fluid as well as serum allergen-specific IgE and IL-4 levels in lung supernatants. On the contrary, regulatory cytokine - IL-10 level - was enhanced. Application of especially ESCs significantly increased the percentage of Treg subsets. Our comparative results showed that i.n. delivery of miRNA-based reprogrammed iPSCs is beneficial in attenuating airway inflammation in a murine model of acute asthma, and that cells also have similar immunomodulatory effects in mice.

Original language	English
Pages (from-to)	31-40
Number of pages	10
Journal	International Immunopharmacology
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/j.intimp.2014.06.011
Publication status	Published - Sept 2014
Externally published	Yes

Funding

This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) [ SBAG-110S368 ] and Marmara University research project BAPKO No: SAG-C-DRP-141112-0333 . We thank Assoc. Prof. Tamer Onder from Koc University for kindly providing us with the pluripotent stem cells and for critically reading the manuscript. We also thank Dr. Aysin Tulunay for her technical assistance, and Hande Bardak and Dr. Elif Aysimi Duman for their critical reading of the manuscript. Ismail Ogulur gratefully acknowledges the grant donated by TUBITAK-BIDEB .

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Pharmacology

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title = "Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma",

abstract = "New strategies are needed to suppress airway inflammation and prevent or reverse airway remodeling in asthma. Reprogramming induced pluripotent stem cells (iPSCs) have the potential of embryonic stem cells (ESCs) and provide a resource for stem cell-based utility. The aim of this study was to evaluate the histopathological and immunomodulatory effects of ESCs and iPSCs for potential allogenic application in a murine model of acute asthma. BALB/c mice were sensitized with alum-absorbed ovalbumin (OVA) and then challenged with 1\% aerosolized OVA. 5 × 105 ESCs and iPSCs were administrated intranasally on the last day of nebulization. Mice were sacrificed after 24 h, and serum allergen specific antibody level, airway remodeling, cytokine levels in lung supernatants, and eosinophilic infiltration in BAL fluid were examined. As a result, more ESCs and iPSCs integrated into the lungs of mice in OVA groups than those of the controls. Epithelial, smooth muscle and basal membrane thicknesses as well as goblet cell hyperplasia occurring in airway remodeling were significantly suppressed by pluripotent stem cells in both distal and proximal airways. Percentage of eosinophils decreased significantly in BAL fluid as well as serum allergen-specific IgE and IL-4 levels in lung supernatants. On the contrary, regulatory cytokine - IL-10 level - was enhanced. Application of especially ESCs significantly increased the percentage of Treg subsets. Our comparative results showed that i.n. delivery of miRNA-based reprogrammed iPSCs is beneficial in attenuating airway inflammation in a murine model of acute asthma, and that cells also have similar immunomodulatory effects in mice.",

author = "Ismail Ogulur and Gulben Gurhan and Kombak, \{Faruk Erdem\} and Deniz Filinte and Isil Barlan and Tunc Akkoc",

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AU - Filinte, Deniz

AU - Barlan, Isil

AU - Akkoc, Tunc

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N2 - New strategies are needed to suppress airway inflammation and prevent or reverse airway remodeling in asthma. Reprogramming induced pluripotent stem cells (iPSCs) have the potential of embryonic stem cells (ESCs) and provide a resource for stem cell-based utility. The aim of this study was to evaluate the histopathological and immunomodulatory effects of ESCs and iPSCs for potential allogenic application in a murine model of acute asthma. BALB/c mice were sensitized with alum-absorbed ovalbumin (OVA) and then challenged with 1% aerosolized OVA. 5 × 105 ESCs and iPSCs were administrated intranasally on the last day of nebulization. Mice were sacrificed after 24 h, and serum allergen specific antibody level, airway remodeling, cytokine levels in lung supernatants, and eosinophilic infiltration in BAL fluid were examined. As a result, more ESCs and iPSCs integrated into the lungs of mice in OVA groups than those of the controls. Epithelial, smooth muscle and basal membrane thicknesses as well as goblet cell hyperplasia occurring in airway remodeling were significantly suppressed by pluripotent stem cells in both distal and proximal airways. Percentage of eosinophils decreased significantly in BAL fluid as well as serum allergen-specific IgE and IL-4 levels in lung supernatants. On the contrary, regulatory cytokine - IL-10 level - was enhanced. Application of especially ESCs significantly increased the percentage of Treg subsets. Our comparative results showed that i.n. delivery of miRNA-based reprogrammed iPSCs is beneficial in attenuating airway inflammation in a murine model of acute asthma, and that cells also have similar immunomodulatory effects in mice.

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Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma

Abstract

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