Intratracheal administration of adipose derived mesenchymal stem cells alleviates chronic asthma in a mouse model

Ranran Dai,Xiaoxia Hou,Guofeng Yan,Guochao Shi,Youchao Yu,Yingmeng Ni

doi:10.1186/s12890-018-0701-x

Ranran Dai, Xiaoxia Hou + Show 4 more

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https://doi.org/10.1186/s12890-018-0701-x

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Abstract

BackgroundAdipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma. However, the underlying mechanism remains unclear. The present study aimed to explore the effects and mechanisms of ASCs on chronic asthma using an ovalbumin (OVA)-sensitized asthmatic mouse model.MethodsMurine ASCs (mASCs) were isolated from male Balb/c mice and identified by the expression of surface markers using flow cytometry. The OVA-sensitized asthmatic mouse model was established and then animals were treated with the mASCs through intratracheal delivery. The therapy effects were assessed by measuring airway responsiveness, performing immuohistochemical analysis, and examining bronchoalveolar lavage fluid (BALF). Additionally, the expression of inflammatory cytokines and lgE was detected by CHIP and ELISA, respectively. The mRNA levels of serum indices were detected using qRT-PCR.ResultsThe mASCs grew by adherence with fibroblast-like morphology, and showed the positive expression of CD90, CD44, and CD29 as well as the negative expression of CD45 and CD34, indicating that the mASCs were successfully isolated. Administering mASCs to asthmatic model animals through intratracheal delivery reduced airway responsiveness, the number of lymphocytes (P < 0.01) and the expression of lgE (P < 0.01), IL-1β (P < 0.05), IL-4 (P < 0.001), and IL-17F (P < 0.001), as well as increased the serum levels of IL-10 and Foxp3, and the percentage of CD4 + CD25 + Foxp3+ Tregs in the spleen, and reduced the expression of IL-17 (P < 0.05) and RORγ.ConclusionsIntratracheal administration of mASCs alleviated airway inflammation, improved airway remodeling, and relieved airway hyperresponsiveness in an OVA-sensitized asthma model, which might be associated with the restoration of Th1/Th2 cell balance by mASCs.

Highlights

Adipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma
The morphological observation of Murine ASCs (mASCs) and the expression of their surface markers The mASCs grew adherent with a fibroblast-like morphology, which gradually transformed to an irregular star shape with further passaging (Fig. 1a)
Effect of mASCs on the pathomorphology of lung tissue in OVA-induced asthma model mice Compared to control mice, OVA-challenged mice showed abnormal lung structure by HE staining, including inverted bronchial mucosa cilia, wall thickening, and swelled mucous membrane, while treatment with mASCs in the OVA group markedly reduced the number of inflammatory cells (Fig. 2a-d)

Summary

Introduction

Adipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma. The present study aimed to explore the effects and mechanisms of ASCs on chronic asthma using an ovalbumin (OVA)-sensitized asthmatic mouse model. As a common chronic respiratory disease, the prevalence of asthma keeps increases every year [1]. The characteristics of asthma include bronchial hyperreactivity and symptoms of airway obstruction [2]. Asthma is not yet cured and clinical symptoms. Multiple types of cells are involved in asthma pathology, including eosinophils, mast cells, T lymphocytes, invariant NKT cells, basophils, type 2 innate lymphoid cells (ILC2s) and others [4]. An imbalance of Th1 lymphocytes/Th2 lymphocytes (Th1/Th2) is thought to be involved in asthma pathogenesis of asthma [5], but this imbalance cannot fully explain the pathological mechanism of asthma.

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