Adipose Tissue-Derived Mesenchymal Stem Cell Modulates the Immune Response of Allergic Rhinitis in a Rat Model.

Nesrine Ebrahim,Ayman Farid,Safwa Sorour,Miriam Safwat,Ahmed Refae,Dina Sabry,Ebtesam Nafie,Yasser Mandour,Amira Mohamed,Radwa Taha

doi:10.3390/ijms20040873

Abstract

This study was designed to investigate the potential effects and underlying mechanism of adipose tissue-derived mesenchymal stem cells (MSCs) on allergic inflammation compared to Montelukast as an antileukotriene drug in a rat model of allergic rhinitis (AR). The effect of MSCs was evaluated in albino rats that were randomly divided into four (control, AR, AR + Montelukast, and AR + MSCs) groups. Rats of AR group were sensitized by ovalbumin (OVA) and then challenged with daily nasal drops of OVA diluted in sterile physiological saline (50 μL/nostril, 100 mg/mL, 10% OVA) from day 15 to day 21 of treatment with/without Montelukast (1 h before each challenge) or MSCs I/P injection (1 × 106 MCSs; weekly for three constitutive weeks). Both Montelukast and MSCs treatment started from day 15 of the experiment. At the end of the 5th week, blood samples were collected from all rats for immunological assays, histological, and molecular biology examinations. Both oral Montelukast and intraperitoneal injection of MSCs significantly reduced allergic symptoms and OVA-specific immunoglobulin E (IgE), IgG1, IgG2a and histamine as well as increasing prostaglandin E2 (PGE2). Further analysis revealed that induction of nasal innate cytokines, such as interleukin (IL)-4 and TNF-α; and chemokines, such as CCL11 and vascular cell adhesion molecule-1 (VCAM-1), were suppressed; and transforming growth factor-β (TGF-β) was up-regulated in Montelukast and MSCs-treated groups with superior effect to MSCs, which explained their underlying mechanism. In addition, the adipose tissue-derived MSCs-treated group had more restoring effects on nasal mucosa structure demonstrated by electron microscopical examination.

Highlights

Mesenchymal stem cells (MSCs) are multipotent cells that are capable of differentiating into three types of mesenchymal cells: adipocytes, osteoblasts, and chondrocytes [1]
Chemical drugs towards allergic rhinitis (AR) are limited to antihistamines, antileukotrienes, and intranasal corticosteroids, which only alleviate allergic symptoms but fail to regulate the allergic reaction
Since AR is characterized as chronic inflammation with eosinophilic infiltration and unbalance between TH1- and TH2-derived cytokines, we propose that mesenchymal stem cells (MSCs)-driven immunomodulation contributes to attenuation of inflammation in AR, improving patient lifestyle [28]

Summary

Introduction

Mesenchymal stem cells (MSCs) are multipotent cells that are capable of differentiating into three types of mesenchymal cells: adipocytes, osteoblasts, and chondrocytes [1]. MSCs represent an important stem cell population with multipotent capabilities that may have high utility for translational clinical applications [2]. MSC-based cell therapy has been demonstrated as a promising strategy in the treatment of immune diseases [3,4]. While the ability of MSCs to modulate immune systems has led to increasing interest in using MSCs as a promising therapeutic modality for allergic airway diseases, only few studies have demonstrated that MSCs can ameliorate allergic airway inflammatory diseases, including asthma [7] and AR [8,9,10]. The immunomodulatory mechanisms of MSCs in allergic airway disease are only partly understood

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