scholarly journals Endometrial Mesenchymal Stem/Stromal Cells: The Enigma to Code Messages for Generation of Functionally Active Regulatory T Cells

2021 ◽  
Author(s):  
Mehdi Aleahmad ◽  
Mahmood Bozorgmehr ◽  
Shohreh Nikoo ◽  
Alireza Ghanavatinejad ◽  
Mohammad-Reza Shokri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Cd4 Cells ◽  
Ifn Γ ◽  
Pre Treatment

Abstract Background Regulatory T cells (Tregs) play an important role in fine tuning immune responses and is pivotal for a successful pregnancy. Recently, the importance of mesenchymal stem cells in regulation of immune responses in general and Tregs in particular has been highlighted. Here, we hypothesized that menstrual stromal/stem cells (MenSCs) contribute to uterine immune system regulation through induction of functionally active Tregs. Methods MenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. The effect of MenSCs on proliferation of anti-CD3/CD28-stimulated T CD4 + cells and generation of Tregs with and without pre-treatment with mitomycin C, IFN-γ and IL-1β was evaluated by flow cytometry. The potential role of IDO, PGE2, IL-6, IL-10, and TGF-β on proliferation of T CD4 + cells and generation of Tregs was assessed using blocking antibodies or agents. IDO activity was evaluated in MenSCs and BMSC culture supernatants by a colorimetric assay. IL-10 and IFN-γ production in MenSCs-primed T CD4 + was measured using intracellular staining. To investigate the functional properties of Tregs induced by MenSCs, Treg cells were isolated and their functional property to inhibit proliferation of anti-CD3/CD28-stimulated PBMCs was assessed by flow cytometry. Results According to the results, proliferation of T CD4 + lymphocytes were enhanced in the presence of MenSCs, while pre-treatment of MenSCs with pro-inflammatory reversed this effect. PGE2 and IDO were the major players in MenSCs-induced T cell proliferation. Non-treated MenSCs decreased frequency of Tregs, whereas after pre-treatment with IFN-γ and IL-1β they induced Tregs, which was mediated through IL-6, IL-10, TGF-β and IDO. IFN-γ/IL-1β-treated MenSCs induced IL-10 and IFN-γ production in CD4 + T cells. Conclusion Collectively, these finding indicates that immunomodulatory impact of menstrual blood stem cells (MenSCs) on generation of Tregs and inhibition of T cells proliferation is largely dependent of pre-treatment with IFN-γ and IL-1β. This is the first report on immunomodulatory impact of MenSCs on Tregs and highlights the pivotal role of endometrial stem cells in regulation of local endometrial immune responses.

scholarly journals Endometrial mesenchymal stem/stromal cells: The Enigma to code messages for generation of functionally active regulatory T cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mehdi Aleahmad ◽  
Mahmood Bozorgmehr ◽  
Shohreh Nikoo ◽  
Alireza Ghanavatinejad ◽  
Mohammad-Reza Shokri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Cd4 Cells ◽  
Ifn Γ ◽  
Pre Treatment

Abstract Background Regulatory T cells (Tregs) play an important role in fine-tuning of immune responses and are pivotal for a successful pregnancy. Recently, the importance of mesenchymal stem cells in regulation of immune responses in general and Tregs in particular has been highlighted. Here, we hypothesized that menstrual stromal/stem cells (MenSCs) contribute to uterine immune system regulation through induction of functionally active Tregs. Methods MenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. The effect of MenSCs on proliferation of anti-CD3/CD28-stimulated T CD4 + cells and generation of Tregs with or without pre-treatment with mitomycin C, IFN-γ and IL-1β was evaluated by flow cytometry. The potential role of IDO, PGE2, IL-6, IL-10, and TGF-β on proliferation of T CD4 + cells and generation of Tregs was assessed using blocking antibodies or agents. IDO activity was evaluated in MenSCs and BMSCs culture supernatants by a colorimetric assay. IL-10 and IFN-γ production in MenSCs-primed T CD4 + was measured using intracellular staining. To investigate the functional properties of Tregs induced by MenSCs, Treg cells were isolated and their functional property to inhibit proliferation of anti-CD3/CD28-stimulated PBMCs was assessed by flow cytometry. Results According to the results, proliferation of T CD4 + lymphocytes was enhanced in the presence of MenSCs, while pre-treatment of MenSCs with pro-inflammatory cytokines reversed this effect. PGE2 and IDO were the major players in MenSCs-induced T cell proliferation. Non-treated MenSCs decreased the frequency of Tregs, whereas after pre-treatment with IFN-γ and IL-1β, they induced functional Tregs with ability to inhibit the proliferation of anti-CD3/CD28-stimulated PBMCs. This effect was mediated through IL-6, IL-10, TGF-β and IDO. IFN-γ/IL-1β-treated MenSCs induced IL-10 and IFN-γ production in CD4 + T cells. Conclusion Collectively, these findings indicate that immunomodulatory impact of menstrual blood stem cells (MenSCs) on generation of Tregs and inhibition of T cells proliferation is largely dependent on pre-treatment with IFN-γ and IL-1β. This is the first report on immunomodulatory impact of MenSCs on Tregs and highlights the pivotal role of endometrial stem cells in regulation of local endometrial immune responses.

Mesenchymal stem cells induce the expansion of regulatory T cells in abortion-prone mice

Reproduction ◽  
2021 ◽  
Author(s):  
Amir Salek Farrokhi ◽  
Amir-Hassan Zarnani ◽  
Fatemeh Rezaei kahmini ◽  
Seyed Mohammad Moazzeni
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
De Novo ◽  
Abortion Rate ◽  
Cellular Mechanisms ◽  
Inguinal Lymph Nodes

Recurrent pregnancy loss (RPL) is one of the most common complications of early pregnancy associated in most cases with local or systemic immune abnormalities such as the diminished proportion of regulatory T cells (Tregs). Mesenchymal stem cells (MSCs) have been shown to modulate immune responses by de novo induction and expansion of Tregs. In this study, we analyzed the molecular and cellular mechanisms involved in Treg-associated pregnancy protection following MSCs administration in an abortion-prone mouse mating. In a case-control study, syngeneic abdominal fat-derived MSCs were administered intraperitoneally (i.p) to the DBA/2-mated CBA/J female mice on day 4.5 of pregnancy. Abortion rate, Tregs proportion in spleen and inguinal lymph nodes, and Ho1, Foxp3, Pd1, and Ctla4 genes expression at the feto-maternal interface were then measured on day 13.5 of pregnancy using flow cytometry and quantitative RT- PCR, respectively. The abortion rate in MSCs-treated mice was significantly reduced and normalized to the level observed in normal pregnant animals. We demonstrated a significant induction of Tregs in inguinal lymph nodes but not in the spleen following MSCs administration. Administration of MSCs remarkably upregulated the expression of HO1, Foxp3, Pd1, and Ctla4 genes in both placenta and decidua. Here, we show that MSCs therapy could protect the fetus in the abortion-prone mice through Tregs expansion and up-regulation of Treg-related genes. These events could establish an immune-privileged microenvironment, which participates in regulation of detrimental maternal immune responses against the semi-allogeneic fetus.

scholarly journals Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-β

2010 ◽  
Vol 184 (10) ◽  
pp. 5885-5894 ◽  
Author(s):  
Shyam A. Patel ◽  
Justin R. Meyer ◽  
Steven J. Greco ◽  
Kelly E. Corcoran ◽  
Margarette Bryan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Regulatory T Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells

scholarly journals Mesenchymal stem cells play an important role in host protective immune responses against malaria by modulating regulatory T cells

2013 ◽  
Vol 43 (8) ◽  
pp. 2070-2077 ◽  
Author(s):  
Reva S. Thakur ◽  
Sultan Tousif ◽  
Vikky Awasthi ◽  
Anirban Sanyal ◽  
P. K. Atul ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Immune Responses

scholarly journals On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation

2012 ◽  
Vol 3 ◽  
Author(s):  
Anja U. Engela ◽  
Carla C. Baan ◽  
Frank J. M. F. Dor ◽  
Willem Weimar ◽  
Martin J. Hoogduijn
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells

scholarly journals Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Function of Allogeneic Activated Vγ9Vδ2 T Lymphocytes In Vitro

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaohuan Liu ◽  
Ting Feng ◽  
Tianxiang Gong ◽  
Chongyang Shen ◽  
Tingting Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Umbilical Cord ◽  
Interleukin 2 ◽  
Cell Contact ◽  
Human Umbilical Cord ◽  
Fas L

Background. Human umbilical cord mesenchymal stem cells (UC-MSCs) can regulate the function of immune cells. However, whether and how UC-MSCs can modulate the function of Vγ9Vδ2 T cells has not been fully understood. Methods. The PBMCs or Vγ9Vδ2 T cells were activated and expanded with pamidronate (PAM) and interleukin-2 (IL-2) with or without the presence UC-MSCs. The effects of UC-MSCs on the proliferation, cytokine expression, and cytotoxicity of Vγ9Vδ2 T cells were determined by flow cytometry. The effects of UC-MSCs on Fas-L, TRAIL-expressing Vγ9Vδ2 T cells, and Vγ9Vδ2 T cell apoptosis were determined by flow cytometry. Results. UC-MSCs inhibited Vγ9Vδ2 T cell proliferation in a dose-dependent but cell-contact independent manner. Coculture with UC-MSCs reduced the frequency of IFNγ+ but increased granzyme B+ Vγ9Vδ2 T cells. UC-MSCs inhibited the cytotoxicity of Vγ9Vδ2 T cells against influenza virus H1N1 infected A549 cells and also reduced the frequency of Fas-L+, TRAIL+ Vγ9Vδ2 T cells but failed to modulate the apoptosis of Vγ9Vδ2 T cells. Conclusions. These results indicated that UC-MSCs efficiently suppressed the proliferation and cytotoxicity of Vγ9Vδ2 T cells and modulated their cytokine production. Fas-L and TRAIL were involved in the regulation. Cell contact and apoptosis of Vγ9Vδ2 T cells were not necessary for the inhibition.

Abstract LB-64: Immune modulatory effects of mesenchymal stem cells on regulatory T cells in mouse glioma model

2014 ◽  
Author(s):  
Kyung-Sub Moon ◽  
Derek A. Wainwright ◽  
Irina V. Balyasnikova ◽  
Chung Kwon Kim ◽  
Yoo Seung Ko ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Regulatory T Cells ◽  
Glioma Model ◽  
Mouse Glioma
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