Abstract

BackgroundEndometrial regenerative cells (ERCs), a novel type of mesenchymal-like stem cell derived from menstrual blood, have been recently evaluated as an attractive candidate source in ulcerative colitis (UC); however, the mechanism is not fully understood. The present study was designed to investigate the effects of ERCs, especially on B-cell responses in UC.MethodsIn this study, colitis was induced by administering 3% dextran sodium sulfate (DSS) via free drinking water for 7 days to BALB/c mice. In the treated group, mice were injected intravenously with 1 × 106 ERCs on days 2, 5, and 8 after DSS induction. Therapeutic effects were assessed by monitoring body weight, disease activity, and pathological changes. Subpopulations of lymphocytes were determined by flow cytometry. IgG deposition in the colon was examined by immunohistochemistry staining. Cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), Western blot, or polymerase chain reaction (PCR) analysis. Adoptive transfer of regulatory B cells (Bregs) into colitis mice was performed.ResultsHere, we demonstrated that ERC treatment prolonged the survival of colitis mice and attenuated disease activity with fewer pathological changes in colon tissue. ERCs decreased the proportion of immature plasma cells in the spleen and IgG deposition in the colon. On the other hand, ERCs increased the production of Bregs and the interleukin (IL)-10 level. Additionally, adoptive transferred Bregs exhibited significant therapeutic effects on colitis mice.ConclusionsIn conclusion, our results unravel the therapeutic role of ERCs on experimental colitis through regulating the B-lymphocyte responses.

Highlights

  • Endometrial regenerative cells (ERCs), a novel type of mesenchymal-like stem cell derived from menstrual blood, have been recently evaluated as an attractive candidate source in ulcerative colitis (UC); the mechanism is not fully understood

  • ERCs attenuated dextran sodium sulfate (DSS)-induced experimental colitis Acute experimental colitis was induced by oral administration of 3% DSS in free drinking water, resulting in severe colitis characterized by body weight loss, bloody diarrhea, and lethargy (Fig. 2a–c)

  • DSS administration lead to the shortening and rigidity of the colon with severe injurious hyperemia and ulceration, which were ameliorated by ERCs (Fig. 2d)

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Summary

Introduction

Endometrial regenerative cells (ERCs), a novel type of mesenchymal-like stem cell derived from menstrual blood, have been recently evaluated as an attractive candidate source in ulcerative colitis (UC); the mechanism is not fully understood. The present study was designed to investigate the effects of ERCs, especially on B-cell responses in UC. Ulcerative colitis (UC) is a chronic, relapsing, and nonspecific inflammatory disorder of the colon, as shown by an imbalance of the immune system to various factors [1]. B cells play a pathogenic role in UC by producing autoantibodies leading to damage of the intestinal epithelium. The topical deficiency of sIgA and a shift from IgA2 to the less stable IgA1 was reported, as well as a significant increase in IgG-producing cells [2]. Perinuclear anti-neutrophil antibodies (p-ANCA) and autoantibodies against tropomyosin are found in the peripheral blood of UC patients, and the numbers of immature plasma cells overexpressing chemokines was increased [3]. The regulatory role of B cells has been demonstrated in many immune disorders including UC, with a

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