Treatment of experimental colitis by endometrial regenerative cells through regulation of B lymphocytes in mice

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.

Stromal Cell-Derived Factor-1 Enhances the Therapeutic Effects of Human Endometrial Regenerative Cells in a Mouse Sepsis Model

“…Furthermore, ERCs do not express MHC class I molecules and only express low levels of MHC class II molecules [10], which enables ERCs with low immunogenicity to function smoothly in mice without rejection. Our research group has validated the therapeutic effects of ERCs in a variety of experimental disease models, such as promoting immune tolerance in cardiac allograft [11], relieving ulcerative colitis injury [12], alleviating acute liver injury [13], mitigating pulmonary fibrosis [14], and lightening renal ischemia-reperfusion injury [15]. However, up to now, we and other groups have not found and reported any case of ERCs rejected by mice.…”

Downregulation of Dickkopf-1 Augments the Therapeutic Effects of Endometrial Regenerative Cells on Experimental Colitis

“…The changed inflammatory mediator profiles, induced by administration of DSS solution, contribute to promoting the immunocyte proliferations or differentiations, disrupting the balance between the immune system and antigens, and thus ultimately render the inflammatory cascade and the destruction in the colonic tissues [52,53]. ERCs, injected into UC paradigms, were reported to have an ability to ameliorate production and accumulation of inflammatory mediators in colons, and thus polish up the immunomodulatory properties in relieving the local tissue injury [20]. But, whether down-regulating DKK1 expression in ERCs, could also modulate the imbalance of inflammatory mediator profiles, and exit a much more provoking effect has not been illustrated till now.…”

“…ERCs were demonstrated to possess the similar phenotypic markers with MSCs, but surmount the limits of traditional MSCs and with more outstanding advantages, including diverse differentiation potentials, immunomodulatory characteristics, non-invasive obtaining process and high proliferative capacity without karyotypic abnormality [19]. We and others have previously reported the forcible therapeutic effects of ERCs for immune-related diseases such as ulcerative colitis, acute liver injury, critical limb ischemia, renal ischemia reperfusion injury, pulmonary fibrosis, myocardial infarction, and so on [20][21][22][23][24][25]. Moreover, there was no serious immunological rejections emerging against xeno-ERCs in these ERCtreated animal models [22].…”

Downregulation of Dickkopf-1 Augments the Therapeutic Effects of Endometrial Regenerative Cells on Experimental Colitis

“…On the contrary, IFN-γ, TNF-α, MPO, COX-2 and iNOs are pro-in ammatory factors which often strongly exacerbate the in ammations cascade in colitis [61][62][63]. ERCs, used for the immune-related diseases, were reported to have an ability to ameliorate the production and accumulation of in ammatory mediators, and thus to relieve the local tissue injury [19,64]. But, whether down-regulating DKK1 expression in ERCs, could also modulate the imbalance of in ammatory mediator pro les, and exit a more provoking effect has not been illustrated till now.…”

“…Compared with MSCs, ERCs were with more outstanding advantages, including diverse differentiation potentials, immunomodulatory properties, non-invasive obtaining process and high proliferative capacity without karyotypic abnormality [18]. We and others have previously reported the forcible therapeutic effects of ERC for immune-related diseases such as ulcerative colitis, acute liver injury, critical limb ischemia, renal ischemia reperfusion injury, pulmonary brosis, myocardial infarction, and so on [19][20][21][22][23][24]. Moreover, no serious immunological rejections were emerging against the human derived ERCs when we used these cells to treat animal models [21].…”