Mechanisms of T-Cell Immunosuppression by Mesenchymal Stromal Cells: What Do We Know So Far?

Haddad, Rodrigo; Saldanha-Araújo, Felipe

doi:10.1155/2014/216806

Cited by 148 publications

(140 citation statements)

References 192 publications

(227 reference statements)

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“…Interestingly, during MSC-mediated immunosuppression of T-cells, the former act through cell-cell interaction, producing soluble factors with anti-inflammatory function and generating Tregs [60]. Indeed, MSCs are able to generate Tregs, in part, by the secretion of TGF-β and by promoting Treg expansion [61,62].…”

Section: Regulatory T-cellsmentioning

confidence: 99%

Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression

Bravo

Carvalho

Saldanha-Araújo

2016

Purinergic Signalling

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Adenosine is an important molecule that exerts control on the immune system, by signaling through receptors lying on the surface of immune cells. This nucleotide is produced, in part, by the action of the ectoenzymes CD39 and CD73. Interestingly, these proteins are expressed on the cell surface of regulatory T-cells (Tregs) and mesenchymal stromal cells (MSCs)-two cell populations that have emerged as potential therapeutic tools in the field of cell therapy. In fact, the production of adenosine constitutes a mechanism used by both cell types to control the immune response. Recently, great scientific progress was obtained regarding the role of adenosine in the inflammatory environment. In this context, the present review focuses on the advances related to the impact of adenosine production over the immune modulatory activity of Tregs and MSCs, and how this nucleotide controls the biological functions of these cells. Finally, we mention the main challenges and hurdles to bring such molecule to clinical settings.

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Section: Regulatory T-cellsmentioning

confidence: 99%

Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression

Bravo

Carvalho

Saldanha-Araújo

2016

Purinergic Signalling

Self Cite

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“…In addition, like Flores AI et al . Stem cell in inflammatory bowel disease bone marrow MSCs, placenta-derived MSCs are nonimmunogenic and immunomodulatory stem cells with high expansion and differentiation capacity [32][33][34][35] . An important issue in using MSCs is their safety.…”

Section: Mesenchymal Stem Cell Transplantationmentioning

confidence: 99%

“…Placental tissues, both fetal (amniotic fluid, Wharton's jelly, amniotic membrane, chorionic villi) and maternal (decidua) represent an important source of MSCs with some advantages including the isolation of large number of cells in a non invasive way [32,33] . In addition, like [32][33][34][35] . An important issue in using MSCs is their safety.…”

mentioning

confidence: 99%

Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy?

Flores¹

2015

WJSC

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Inflammatory bowel diseases are inflammatory, chronic and progressive diseases of the intestinal tract for which no curative treatment is available. Research in other fields with stem cells of different sources and with immunoregulatory cells (regulatory T-lymphocytes and dendritic T-cells) opens up new expectations for their use in these diseases. The goal for stem cell-based therapy is to provide a permanent cure. To achieve this, it will be necessary to obtain a cellular product, original or genetically modified, that has a high migration capacity and homes into the intestine, has high survival after transplantation, regulates the immune reaction while not being visible to the patient's immune system, and repairs the injured tissue. Core tip: Inflammatory bowel diseases are inflammatory, chronic and progressive diseases of the intestinal tract. A limited experience is available with hematopoietic and mesenchymal stem cell transplantation for the treatment of these conditions. Research is ongoing with other cell lines which have been used in conditions alike to inflammatory bowel disease and which will possibly have a therapeutic role in this condition. INTRODUCTIONInflammatory bowel disease (IBD) mainly consists of two clinical conditions, Crohn's disease (CD) and ulcerative colitis (UC). It is mainly characterized by chronic, destructive inflammation of the gastrointestinal tract for which no curative treatment is currently available.Its etiology is unknown, but it is accepted that it could be the result of loss of tolerance to intraluminal bowel antigens [1] . Genetic, environmental, and microbiological factors are involved in its development, Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy?Ana I Flores, Gonzalo J Gómez-Gómez, Ángeles Masedo-González, M Pilar Martínez-Montiel together with morphological and functional changes in the intestinal barrier associated to an impaired immune response [2] . Early data supporting genetic involvement in the pathogenesis of IBD come from familial clinical studies showing a greater incidence in twins [3,4] , first-degree relatives [5,6] and given ethnic groups [7,8] . Genome-wide association scan studies have allowed for identification of more than 163 loci associated to IBD [9] , 73 genes associated to CD and 47 to UC [10] , and overlapping genes for both conditions have also been found [11] . Genetic factors would however account for less than 25% of cases [12] . The exception is represented by a monogenic disorder referred to as IBD-like diseases, which are associated with severe colitis in childhood and have at most three loci alternatives [13] . On the other hand the increase of the incidence of IBD suggests that environmental factors are more important than genetic factors in the development of IBD [14] . Since IBD etiology is currently unknown, current treatment is intended to control the inflammatory intestinal process, thus avoiding irreversible structural damage. However, current therapeutic results are di...

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“…These cells can migrate to damaged or inflamed sites and secrete a variety of bioactive molecules, such as cytokines and growth factors, and induce angiogenic, antiscarring, chemoattractant, and immunomodulatory effects [da Silva Meirelles et al, 2009]. Phenotypically, MSCs express low levels of major histocompatibility complex (MHC) class I molecules and lack the surface expression of MHC class II and costimulatory molecules [Nauta and Fibbe, 2007;Haddad and Saldanha-Araujo, 2014]. These features make MSCs immunoprivileged cells that can be transplanted to an MHC-mismatched recipient and induce immunological tolerance.…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Biological and Functional Properties of Bone Marrow Mesenchymal Stromal Cells Expanded in Media with Different Platelet Lysate Content

Škifić

Golemović

Crkvenac-Gornik

et al. 2018

Cells Tissues Organs

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Due to their ability to induce immunological tolerance in the recipient, mesenchymal stromal cells (MSCs) have been utilized in the treatment of various hematological and immune- and inflammation-mediated diseases. The clinical application of MSCs implies prior in vitro expansion that usually includes the use of fetal bovine serum (FBS). The present study evaluated the effect of different platelet lysate (PL) media content on the biological properties of MSCs. MSCs were isolated from the bone marrow of 13 healthy individuals and subsequently expanded in three different culture conditions (10% PL, 5% PL, 10% FBS) during 4 passages. The cells cultured in different conditions had comparable immunophenotype, clonogenic potential, and differentiation capacity. However, MSC growth was significantly enhanced in the presence of PL. Cultures supplemented with 10% PL had a higher number of cumulative population doublings in all passages when compared to the 5% PL condition (p < 0.03). Such a difference was also observed when 10% PL and 10% FBS conditions were compared (p < 0.005). A statistically significant difference in population doubling time was determined only between the 10% PL and 10% FBS conditions (p < 0.005). Furthermore, MSCs cultured in 10% PL were able to cause a 66.9% reduction of mitogen-induced lymphocyte proliferation. Three chromosome aberrations were detected in PL conditions. Since two changes occurred in the same do nor, it is possible they were donor dependent rather than caused by the culture condition. These findings demonstrate that a 10% PL condition enables a higher yield of MSCs within a shorter time without altering MSC properties, and should be favored over the 5% PL condition.

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Mechanisms of T-Cell Immunosuppression by Mesenchymal Stromal Cells: What Do We Know So Far?

Cited by 148 publications

References 192 publications

Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression

Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression

Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy?

Comparative Analysis of Biological and Functional Properties of Bone Marrow Mesenchymal Stromal Cells Expanded in Media with Different Platelet Lysate Content

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