scholarly journals SDF-1/CXCR4 axis enhances the immunomodulation of human endometrial regenerative cells in alleviating experimental colitis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiang Li ◽  
Xu Lan ◽  
Yiming Zhao ◽  
Grace Wang ◽  
Ganggang Shi ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
Endometrial Regenerative Cells ◽  
Regenerative Cells ◽  
Cxcr4 Axis

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

2020 ◽  
Author(s):  
Dingding Yu ◽  
Yiming Zhao ◽  
Yonghao Hu ◽  
Dejun Kong ◽  
Wang Jin ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tap Water ◽  
Body Weight Loss ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Endometrial Regenerative Cells ◽  
Tnf Α ◽  
Regenerative Cells ◽  
Dickkopf 1

Abstract Background We have demonstrated that endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and can attenuate experimental colitis, however, its underlying mechanism needs further investigation. Dickkopf-1 (DKK1), a glucoprotein secreted by mesenchymal stromal cells (MSCs), is a classical inhibitor of Wnt/β-catenin pathway which is closely associated with the development of colitis. Therefore, the objective of this study was to investigate whether ERCs could also secret DKK1, and whether the downregulation of DKK1 (DKK1low-ERCs) would enhance the therapeutic effects of ERCs in attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. Unmodified ERCs, IL-1β-treated ERCs (DKK1low-ERCs) and glucocorticoid-treated ERCs (DKK1high-ERCs) were injected (1 million/mouse/day, i.v.) on day 2, 5 and 8 respectively. Colonic and splenic samples were harvested on day 10 after DSS-induction. Results It was found that DKK1low-ERC treatment markedly attenuated colonic damage, body weight loss and colon-length shortening in colitis mice. Compared with other treatments, cell populations of CD4+IL-4+Th2, CD4+CD25+FOXP3+Treg, and CD68+CD206+macrophages in spleens were also significantly upregulated in DKK1low-ERC group (p < 0.05). In addition, lower expression of pro-inflammatory (TNF-α and IFN-γ), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) and β-catenin were detected in colons in DKK1low-ERC group (p < 0.01 vs. other groups). Conclusions DKK1low-ERCs display augmented immunoregulatory ability and therapeutic effects in DSS-induced colitis.

scholarly journals Endometrial regenerative cells as a novel cell therapy attenuate experimental colitis in mice

2014 ◽  
Vol 12 (1) ◽  
Author(s):  
Yongcheng Lv ◽  
Xiaoxi Xu ◽  
Bai Zhang ◽  
Guangying Zhou ◽  
Hongyue Li ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Experimental Colitis ◽  
Endometrial Regenerative Cells ◽  
Regenerative Cells

scholarly journals IL-1β pre-stimulation enhances the therapeutic effects of endometrial regenerative cells on experimental colitis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dingding Yu ◽  
Yiming Zhao ◽  
Hongda Wang ◽  
Dejun Kong ◽  
Wang Jin ◽  
...  
Keyword(s):  
Tap Water ◽  
Treatment Strategies ◽  
Body Weight Loss ◽  
Experimental Colitis ◽  
Treated Group ◽  
Current Treatment ◽  
Th2 Cells ◽  
Therapeutic Effects ◽  
Endometrial Regenerative Cells ◽  
Regenerative Cells

Abstract Background Ulcerative colitis (UC) is a chronic, relapsing, and non-specific inflammatory bowel disease, and the current treatment strategies were mainly used to relieve symptoms or for maintenance. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and have been demonstrated to alleviate multiple immune-dysregulation diseases. Pro-inflammatory stimuli were reported to enhance the immunosuppressive functions of ERCs, but the mechanism underlined is not fully understood. Here, we have designed this study to investigate the therapeutic effects of IL-1β-primed ERCs in the attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. PBS (200 μL), ERCs, and IL-1β-primed ERCs (10ng/mL, 48 h) were injected (1 million/mouse/day, i.v.) on day 2, 5, and 8, respectively. Colonic and splenic samples were harvested on day 10 after DSS induction. Results It was found that IL-1β-primed ERC treatment markedly attenuated colonic damage, body weight loss, and colon length shortening in colitis mice. Compared with other treatments, cell populations of CD4+IL-4+Th2 cells, CD4+CD25+FOXP3+ regulatory T cells (Tregs), and CD68+CD206+ macrophages in spleens were also significantly upregulated in the IL-1β-primed ERC-treated group (p < 0.05). In addition, lower expression of pro-inflammatory (IFN-γ, IL-17, TNF-α, and IL-6), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) were detected in colons in the IL-1β-primed ERC-treated group (p < 0.05 vs. other groups). Importantly, we also found that different generations of ERCs had an overall lower secretion of Dickkopf-1 (DKK1) by IL-1β pre-stimulation (p < 0.05) and a higher expression of β-catenin in colonic and splenic tissues after the administration of IL-1β-primed ERCs. Conclusions This study has demonstrated that IL-1β pre-stimulation effectively downregulated DKK1 expression in ERCs, which in turn promoted the wnt/β-catenin pathway activation in colonic and splenic tissues. Consequently, IL-1β-primed ERCs exhibited an enhanced therapeutic effect in the attenuation of DSS-induced colitis.

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

2020 ◽  
Author(s):  
Dingding Yu ◽  
Yiming Zhao ◽  
Yonghao Hu ◽  
Dejun Kong ◽  
Wang Jin ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tap Water ◽  
Body Weight Loss ◽  
Experimental Colitis ◽  
Underlying Mechanism ◽  
Therapeutic Effects ◽  
Endometrial Regenerative Cells ◽  
Tnf Α ◽  
Regenerative Cells ◽  
Dickkopf 1

Abstract Background We have demonstrated that endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and can attenuate experimental colitis, however, its underlying mechanism needs further investigation. Dickkopf-1 (DKK1), a glucoprotein secreted by mesenchymal stromal cells (MSCs), is a classical inhibitor of Wnt/β-catenin pathway which is closely associated with the development of colitis. Therefore, the objective of this study was to investigate whether ERCs could also secret DKK1, and whether the downregulation of DKK1 (DKK1 low -ERCs) would enhance the therapeutic effects of ERCs in attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. Unmodified ERCs, IL-1β-treated ERCs (DKK1 low -ERCs) and glucocorticoid-treated ERCs (DKK1 high -ERCs) were injected (1 million/mouse/day, i.v. ) on day 2, 5 and 8 respectively. Colonic and splenic samples were harvested on day 10 after DSS-induction. Results It was found that DKK1 low -ERC treatment markedly attenuated colonic damage, body weight loss and colon-length shortening in colitis mice. Compared with other treatments, cell populations of CD4 + IL-4 + Th2, CD4 + CD25 + FOXP3 + Treg, and CD68 + CD206 + macrophages in spleens were also significantly upregulated in DKK1 low -ERC group ( p < 0.05). In addition, lower expression of pro-inflammatory (TNF-α and IFN-γ), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) and β-catenin were detected in colons in DKK1 low -ERC group ( p < 0.01 vs. other groups). Conclusions DKK1 low -ERCs display augmented immunoregulatory ability and therapeutic effects in DSS-induced colitis.

scholarly journals Blockade of CXCL12/CXCR4 Axis Ameliorates Murine Experimental Colitis

2008 ◽  
Vol 327 (2) ◽  
pp. 383-392 ◽  
Author(s):  
Sakae Mikami ◽  
Hiroshi Nakase ◽  
Shuji Yamamoto ◽  
Yasuhiro Takeda ◽  
Takuya Yoshino ◽  
...  
Keyword(s):  
Experimental Colitis ◽  
Cxcr4 Axis

scholarly journals Endometrial regenerative cells for treatment of heart failure: a new stem cell enters the clinic

2013 ◽  
Vol 11 (1) ◽  
pp. 56 ◽  
Author(s):  
Leo Bockeria ◽  
Vladimir Bogin ◽  
Olga Bockeria ◽  
Tatyana Le ◽  
Bagrat Alekyan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cell ◽  
Endometrial Regenerative Cells ◽  
Regenerative Cells

scholarly journals Endometrial regenerative cells: A novel stem cell population

2007 ◽  
Vol 5 (1) ◽  
Author(s):  
Xiaolong Meng ◽  
Thomas E Ichim ◽  
Jie Zhong ◽  
Andrea Rogers ◽  
Zhenglian Yin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Population ◽  
Stem Cell Population ◽  
Endometrial Regenerative Cells ◽  
Regenerative Cells

scholarly journals Galectin-9 is required for endometrial regenerative cells to induce long-term cardiac allograft survival in mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yiming Zhao ◽  
Xiang Li ◽  
Dingding Yu ◽  
Yonghao Hu ◽  
Wang Jin ◽  
...  
Keyword(s):  
Cell Activation ◽  
Cardiac Allograft ◽  
Mouse Heart ◽  
Dependent Manner ◽  
Allograft Survival ◽  
Endometrial Regenerative Cells ◽  
Treg Population ◽  
Regenerative Cells

Abstract Background Endometrial regenerative cells (ERCs), a novel type of mesenchymal-like stem cells, were identified as an attractive candidate for immunoregulation and induction of cardiac allograft tolerance. However, the underlying mechanisms of ERCs in immune regulation still remain largely unclear. The present study is designed to determine whether the expression of Galectin-9 (Gal-9), a soluble tandem-repeat member of the galectin family, is crucial for ERC-based immunomodulation. Methods In this study, we measured Gal-9 expression on ERCs and then co-cultured Gal-9-ERCs, ERCs, and ERCs+lactose (Gal-9 blocker) with activated C57BL/6-derived splenocytes. Furthermore, we performed mouse heart transplantation between BALB/c (H-2d) donor and C57BL/6 (H-2b) recipient. ERCs were administrated 24 h after the surgery, either alone or in combination with rapamycin. Results Our data demonstrate that ERCs express Gal-9, and this expression is increased by IFN-γ stimulation in a dose-dependent manner. Moreover, both in vitro and in vivo results show that Gal-9-ERC-mediated therapy significantly suppressed Th1 and Th17 cell response, inhibited CD8+ T cell proliferation, abrogated B cell activation, decreased donor-specific antibody production, and enhanced the Treg population. The therapeutic effect of ERCs was further verified by their roles in prolonging cardiac allograft survival and alleviating graft pathological changes. Conclusions Taken together, these data indicate that Gal-9 is required for ERC-mediated immunomodulation and prevention of allograft rejection.

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