Abstract

No effective therapeutic strategies have been developed against food allergies. Immunomodulation during early infant period could prevent the development of food allergies. We investigated the preventive effects of human hematopoietic mesenchymal stem cells (hHMSCs) in mice with ovalbumin (OVA)-induced food allergy. BALB/c mice with OVA-induced food allergy were divided into 3 groups, and each group was treated with hHMSCs or hHMSC culture medium (hHMSC-CM) or saline. Ear thickness, allergy score, rectal temperature, and diarrhea occurrence were checked. Total IgE, OVA-specific IgE, and mucosal mast cell protease-1 (mMCP-1) were measured by ELISA. Other allergic parameters were analyzed using histology specimens, RT-PCR, and flow cytometry. Treatment with hHMSCs or hHMSC-CM significantly suppressed the frequency of anaphylactic response and rectal temperature decline, reduced diarrhea, total IgE, OVA-specific IgE, and mMCP-1. While the treatment decreased the level of Th2 cytokines, it enhanced IL-10 and TGF-β1 mRNA. Exposure to hHMSC or hHMSC-CM did not generate regulatory T cells, but reduced mast cells. The immunomodulatory effect on the Th2 cytokines was greater in hHMSC-CM than in hHMSCs. hHMSC treatment may be a promising preventive intervention against food allergy. Further studies are needed to elucidate the key substances released from hHMSC to induce immune tolerance.

Highlights

  • We investigated the effect of hematopoietic mesenchymal stem cells (hHMSCs) and hHMSC culture medium on alleviation of clinical allergic response

  • Diarrhea and anaphylactic responses in the OVA mice were improved in both hHMSC mice and hHMSC-CM mice

  • Effects of intervention on both allergy scoring and diarrhea were higher in the hHMSC-CM mice

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. IgE-mediated food allergy can be recognized from patients and physicians because the symptoms immediately develop after exposure to food allergen. In the asthmatic mouse model, intravenous injection of bone marrow-derived MSCs decreased the levels of total IgE, IL-5, and IL-13 [7], human-induced pluripotent stem cells decreased the levels of OVA-specific IgE, IgG, IL-4, IL-5, and IL-13 [16], and placenta-derived MSCs increased IL-10 and regulatory T (Treg) cells [17] in the serum. In a mouse model of allergic conjunctivitis, topical administration of TNF-α-stimulated bone marrow-derived MSC culture medium decreased mast cell activity, IgE, and histamine levels [22]. In an AD mouse model, intravenous administration of MSCs reduced IgE levels in the serum, inhibited B cell differentiation, T cell activities, and cytokine production [6].

Sensitization and Challenge with OVA in a Mouse Model
Process
Clinical Symptoms
Histopathological Analysis
Measurements of Cytokines and Chemokines by qPCR
Flow Cytometry
Statistical Analysis
Results
4.4.Discussion
Full Text
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