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. 2022 Feb 21;10(2):511.
doi: 10.3390/biomedicines10020511.

Preventive Effects of a Human Hematopoietic Mesenchymal Stem Cell (hHMSC) Therapy in Ovalbumin-Induced Food Allergy

Dong-Geon Lee  1 , Yu-Jin Lee  1 , Song-Hee Park  1 , Hye-Ree Park  1 , Hoon Kang  1 , Jung-Eun Kim  1
Affiliations

Preventive Effects of a Human Hematopoietic Mesenchymal Stem Cell (hHMSC) Therapy in Ovalbumin-Induced Food Allergy

Dong-Geon Lee et al. Biomedicines. .

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.

Keywords: food allergy; human mesenchymal stem cell; prevention.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Process of allergic sensitization to food in mice with OVA, MSC, or MSC CM is shown. MSC, mesenchymal stem cell; MSC CM, mesenchymal stem cell culture medium; OVA, Ovalbumin.
Figure 2
Figure 2
OVA challenge elevated immunoglobulin and mMCP-1 levels and MSC or MSC CM reversed the change. Concentrations of (A) total IgE, (B) OVA-specific IgE, (C) OVA-specific IgG, and (D) mMCP-1 in the serum measured by ELISA are shown. Each value indicates mean ± standard error of the mean. ## p < 0.01 versus CTL, * p < 0.05 versus OVA, ** p < 0.01 versus OVA. CTL, control; Ig, immunoglobulin; mMCP, mucosal mast cell protease; MSC, mesenchymal stem cell; MSC CM, mesenchymal stem cell culture medium; OVA, Ovalbumin.
Figure 3
Figure 3
OVA challenge upregulated inflammatory cytokines and IL-10 transcription and MSC or MSC CM reversed the change in the ear skin. (A) IL-4, (B) IL-5, (C) IL-13, (D) IL-10, (E) TGF-β1, (F) IL-23α, and (G) IL-31 mRNA level changes in the ear skin measured by qPCR are shown. Each value indicates mean ± standard error of the mean. # p < 0.05 versus CTL, ## p < 0.01 versus CTL, * p < 0.05 versus OVA, ** p < 0.01 versus OVA. CTL, control; IL, interleukin; MSC, mesenchymal stem cell; MSC CM, mesenchymal stem cell culture medium; OVA, Ovalbumin; qPCR, quantitative polymerase chain reaction; TGF, transforming growth factor.
Figure 4
Figure 4
OVA challenge upregulated inflammatory cytokines and IL-10 transcription, downregulated TGF- β1 and MSC or MSC CM reversed the change in the SI. (A) IL-4, (B) IL-5, (C) IL-13, (D) IL-10, (E) TGF-β1, (F) IL-23α, (G) IL-31, (H) IL-12α, and (I) IFN-γ mRNA level changes in the SI measured by qPCR are shown. Each value indicates mean ± standard error of the mean. # p < 0.05 versus CTL, * p < 0.05 versus OVA, CTL, control; IL, interleukin; MSC, mesenchymal stem cell; MSC CM, mesenchymal stem cell culture medium; OVA, Ovalbumin; qPCR, quantitative polymerase chain reaction; SI, small intestine; TGF, transforming growth factor.
Figure 5
Figure 5
OVA challenge increased IgE+ c-kit+ mast cells and MSC or MSC CM reversed the change in the ear skin, mLN, and SI tissue. IgE+ c-kit+ mast cells in the (A) ear skin, (B) mLN, and (C) SI tissue measured by flow cytometry are shown. Mean percentage (mast cell counts/total cell counts) is shown in the right upper side. Ig, immunoglobulin; mLN, mesenteric lymph node; MSC, mesenchymal stem cell; MSC CM, mesenchymal stem cell culture medium; OVA, Ovalbumin; SI, small intestine.
Figure 6
Figure 6
OVA challenge increased CD4+ Foxp3+ T cells and MSC or MSC CM reversed the change in the ear skin, mLN, and SI tissue. CD4+ Foxp3+ T cells in the (A) ear skin, (B) mLN, and (C) SI tissue measured by flow cytometry are shown. Mean percentage (CD4+ Foxp3+ T cell counts/total cell counts) is shown in the right upper side. CD, cluster of differentiation; Fox, forkhead box; mLN, mesenteric lymph node; MSC, mesenchymal stem cell; MSC CM, mesenchymal stem cell culture medium; OVA, Ovalbumin; SI, small intestine.
Figure 7
Figure 7
OVA challenge induced inflammation and mast cell infiltration in the tissue and MSC or MSC CM attenuated the change in the ear skin, SI, and spleen. Histological changes of (A) ear skin, (B) SI, or (C) spleen are shown. Sections are stained with H&E (hematoxylin and eosin, ear skin ×100, ×200, SI, ×100, ×200, spleen ×100) or Toluidine blue (×200). Mast cells are indicated by red arrows. H&E, hematoxylin, and eosin; MSC, mesenchymal stem cell; MSC CM, mesenchymal stem cell culture medium; OVA, Ovalbumin; SI, small intestine.
Figure 8
Figure 8
No significant changes of villus/crypt length ratio were observed in the colon with OVA, MSC, or MSC CM. Villus/crypt length ratio of colon is shown. Each value indicates mean ± standard error of the mean. MSC, mesenchymal stem cell; MSC CM, mesenchymal stem cell culture medium; OVA, Ovalbumin.
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