Mesenchymal Stem Cells: Immunology and Therapeutic Benefits

Haddad, Najib El

doi:10.5772/21933

Cited by 7 publications

(4 citation statements)

References 144 publications

(192 reference statements)

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“…MSCs are not immunogenic since they fail to elicit a proliferative response in allogeneic lymphocytes [ 44 , 48 , 56 ]. Also, in-vivo investigations proved the persistence of MSCs while infused to the immunocompetent recipient after transplantation [ 4 , 27 ]. MSCs do not express FAS ligand or costimulatory molecules, such as B7-1, B7-2, CD40, or CD40L.…”

Section: Discussionmentioning

confidence: 99%

Induction of CD4+CD25+FOXP3+ regulatory T cells by mesenchymal stem cells is associated with modulation of ubiquitination factors and TSDR demethylation

et al. 2018

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BackgroundMesenchymal stem cells (MSCs) are known for their ability to induce the conversion of conventional T cells (Tconvs) into induced regulatory T cells (iTregs) in specific inflammatory contexts. Stable Foxp3 expression plays a major role in the phenotypic and functional stability of iTregs. However, how MSCs induce stable Foxp3 expression remains unknown.MethodsWe first investigated the role of cell–cell contact and cytokine secretion by bone marrow-derived MSCs (BM-MSCs) on the induction, stability, and suppressive functions of Tregs under various experimental conditions that lead to Foxp3 generation by flow cytometry and ELISA respectively. Second, we studied the effect of MSCs on TRAF6, GRAIL, USP7, STUB1, and UBC13 mRNA expression in CD4+ T cells in correlation with the suppressive function of iTregs by real-time PCR; also, we investigated Foxp3 Treg-specific demethylated region (TSDR) methylation in correlation with Foxp3 stability by the high-resolution melting technique. Third, we studied the effect of ex-vivo-expanded BM-MSCs on the induction of transplant tolerance in a model of fully allogeneic skin transplantation. We further analyzed the cytokine secretion patterns in grafted mice as well as the mRNA expression of ubiquitination genes in CD4+ T cells collected from the spleens of protected mice.ResultsWe found that in-vitro MSC-induced Tregs express high mRNA levels of ubiquitination genes such as TRAF6, GRAIL, and USP7 and low levels of STUB1. Moreover, they have enhanced TSDR demethylation. Infusion of MSCs in a murine model of allogeneic skin transplantation prolonged allograft survival. When CD4+ T cells were harvested from the spleens of grafted mice, we observed that mRNA expression of the Foxp3 gene was elevated. Furthermore, Foxp3 mRNA expression was associated with increased TRAF6, GRAIL, UBC13, and USP7 and decreased STUB1 mRNA levels compared with the levels observed in vitro.ConclusionsOur data suggest a possible ubiquitination mechanism by which MSCs convert Tconvs to suppressive and stable iTregs.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0991-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Induction of CD4+CD25+FOXP3+ regulatory T cells by mesenchymal stem cells is associated with modulation of ubiquitination factors and TSDR demethylation

et al. 2018

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“…Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from many tissues, and they have different types, such as chondrocyte, adipocyte or osteocyte (El, 2011). MSCs also have strong immunomodulation abilities; e.g., they suppress immune cells through the secretion of cytokines, such as prostaglandin E2 (PGE2), indoleamine 2,3 dioxygenase (IDO), hepatocyte growth factor (HGF), and soluble human leukocyte antigen G (sHLA-G) and transform growth factor beta (TGF-b) and interleukin 10 (IL-10) (Budoni et al, 2013;Özdemir et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…The immunomodulatory effects of MSCs occur in a non-specific and nonselective manner. When MSCs are activated, they produce certain cytokines, such as PGE2, IDO, HGF, TGF-b and IL-10, which suppress almost all immune cells (El, 2011;Özdemir et al, 2016;Cho et al, 2014). However, this suppressive effect only lasts for the lifespan of MSCs.…”

Section: Introductionmentioning

confidence: 99%

The investigation of immunomodulatory effects of adipose tissue mesenchymal stem cell educated macrophages on the CD4 T cells

Özdemir¹,

Özdemir²,

Sarıboyacı³

et al. 2019

Immunobiology

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Keywords:Mesenchymal stem cell M1 macrophage M2 macrophage Th1 Th2 Th17 Treg Immunomodulation A B S T R A C T Mesenchymal stem cells (MSCs) are strong immunomodulatory cells investigated in numerous clinical studies on fatal pathologies, such as graft versus host disease and autoimmune diseases; e.g., systemic lupus erythematosus, Crohn's disease, and ulcerative colitis. Macrophages are one of the critical cells linking the innate and adaptive immune system, and it has been shown that MSCs can differentiate between pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype of macrophages. However, it has not yet been fully clarified whether these differentiated macrophages are functional. In this study, we compared the immunomodulatory effects on the CD4 T cells of M1, M2a and M2c macrophages with the macrophages that directly and indirectly cultured with MSCs. We analyzed the changes in CD14, CD64, CD80, CD163 and CD200R expression to evaluate macrophage phenotypes, and the changes in CD4, IFN-g, IL-4, IL-17a and FoxP3 expression to evaluate T helper subsets using the FACS method. The changes in IL-1b, IL-4, IL-10, IL-12p70, IL-17a and IFN-g in the media supernatants were analyzed using the Luminex method. We also performed WST-1 and Caspase-3 ELISA analyses to observe the proliferation and apoptosis status of the T cells. MSCs were found to differentiate macrophages into a distinctive phenotype, which was close to the M2c phenotype, but was not considered as an M2c cell due to the low expression of CD163, a characteristic marker for M2c. While MEM-D, MEM-ID and MSCs showed similar inhibitory effects on the Th2 and Th17 cells, the most significant increase in Treg cell frequencies was seen in MEM-D cells. Macrophages can alter their phenotypes and functions according to the stimuli from the environment. The fact that macrophages educated with MSCs suppressed the production of all the cytokines we evaluated even after the removal of MSCs suggests that these cells may be differentiated by MSCs into a suppressive macrophage subgroup. However, the Treg cell activation caused by direct interactions between MSCs and macrophage cells may be the most prominent observation of this study compared to previous work. As a result, according to our data, the interactions between MSCs and macrophages may lead to differentiation of macrophage cells into an immunosuppressive phenotype, and these macrophages may suppress the T lymphocyte subgroups at least as effectively as MSCs. However, our data obtained from in vitro experiments should be supported by future in vivo studies.

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“…(HU et al, 2013). Para além da supressão da resposta imune pela modulação da proliferação e ativação das células T, as MSCs também modulam a atividade das células B, monócitos, macrófagos e outros intervenientes que medeiam o sistema imunológico (HADDAD et al, 2011;LANGE-CONSIGLIO et al, 2013;PLOCK et al, 2013;SOHNI;VERFAILLIE, 2013;INSAUSTI et al, 2014). Salientar que, embora não se tenha observado uma variação significativa dos linfócitos na contagem diferencial das células brancas, registrou-se uma modesta redução ao longo do tratamento.…”

Section: Injeção Endovenosa Das Amscsunclassified

<b>Modelo clínico de uso de células-tronco mesenquimais da membrana amniótica para o tratamento da insuficiência renal crônica em gatos</b>

Vidane¹

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Mesenchymal Stem Cells: Immunology and Therapeutic Benefits

Cited by 7 publications

References 144 publications

Induction of CD4+CD25+FOXP3+ regulatory T cells by mesenchymal stem cells is associated with modulation of ubiquitination factors and TSDR demethylation

Induction of CD4+CD25+FOXP3+ regulatory T cells by mesenchymal stem cells is associated with modulation of ubiquitination factors and TSDR demethylation

The investigation of immunomodulatory effects of adipose tissue mesenchymal stem cell educated macrophages on the CD4 T cells

<b>Modelo clínico de uso de células-tronco mesenquimais da membrana amniótica para o tratamento da insuficiência renal crônica em gatos</b>

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