Abstract
IntroductionThe ability to self-renew, be easily expanded in vitro and differentiate into different mesenchymal tissues, render mesenchymal stem cells (MSCs) an attractive therapeutic method for degenerative diseases. The subsequent discovery of their immunosuppressive ability encouraged clinical trials in graft-versus-host disease and auto-immune diseases. Despite sharing several immunophenotypic characteristics and functional capabilities, the differences between MSCs arising from different tissues are still unclear and the published data are conflicting.MethodsHere, we evaluate the influence of human MSCs derived from umbilical cord matrix (UCM), bone marrow (BM) and adipose tissue (AT), co-cultured with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (MNC), on T, B and natural killer (NK) cell activation; T and B cells’ ability to acquire lymphoblast characteristics; mRNA expression of interleukin-2 (IL-2), forkhead box P3 (FoxP3), T-bet and GATA binding protein 3 (GATA3), on purified T cells, and tumor necrosis factor-alpha (TNF-α), perforin and granzyme B on purified NK cells.ResultsMSCs derived from all three tissues were able to prevent CD4+ and CD8+ T cell activation and acquisition of lymphoblast characteristics and CD56dim NK cell activation, wherein AT-MSCs showed a stronger inhibitory effect. Moreover, AT-MSCs blocked the T cell activation process in an earlier phase than BM- or UCM-MSCs, yielding a greater proportion of T cells in the non-activated state. Concerning B cells and CD56bright NK cells, UCM-MSCs did not influence either their activation kinetics or PHA-induced lymphoblast characteristics, conversely to BM- and AT-MSCs which displayed an inhibitory effect. Besides, when co-cultured with PHA-stimulated MNC, MSCs seem to promote Treg and Th1 polarization, estimated by the increased expression of FoxP3 and T-bet mRNA within purified activated T cells, and to reduce TNF-α and perforin production by activated NK cells.ConclusionsOverall, UCM-, BM- and AT-derived MSCs hamper T cell, B cell and NK cell-mediated immune response by preventing their acquisition of lymphoblast characteristics, activation and changing the expression profile of proteins with an important role in immune function, except UCM-MSCs showed no inhibitory effect on B cells under these experimental conditions. Despite the similarities between the three types of MSCs evaluated, we detect important differences that should be taken into account when choosing the MSC source for research or therapeutic purposes.
Highlights
The ability to self-renew, be expanded in vitro and differentiate into different mesenchymal tissues, render mesenchymal stem cells (MSCs) an attractive therapeutic method for degenerative diseases
MSCs prevent T and B cells’ acquisition of lymphoblast characteristics, except for umbilical cord matrix (UCM)-MSCs that are unable to inhibit this process in B and CD56bright natural killer (NK) cells Lymphocytes undergo multiple rounds of clonal division after mitogenic stimulation
mononuclear cells (MNC) were co-cultured with bone marrow (BM), UCM- and adipose tissue (AT)-MSCs at the ratio of 10:1, in the presence of PHA
Summary
The ability to self-renew, be expanded in vitro and differentiate into different mesenchymal tissues, render mesenchymal stem cells (MSCs) an attractive therapeutic method for degenerative diseases. MSCs can be isolated from adult tissues, such as bone marrow, adipose tissue, endometrial polyps, menstrual blood and so on [2], and from fetal tissues, such as placenta, umbilical cord blood and matrix [8,9] Their ability to differentiate into different tissues is variable according to their tissue of origin [4]. Other interesting characteristics are that MSCs can migrate and home to tissues and organs in response to growth factors, cytokines, chemokines or adhesion molecules and, therein, mediate immunomodulatory actions [10,14,16,17,18] Due to their multipotency, MSC are a very attractive choice for clinical applications in several immune disorders, such as arthritis, encephalomyelitis, systemic lupus erythematosus, and in regenerative diseases, including diabetes and skin grafting [8,10,13,16,19]. There are studies reporting that a separation of MSCs and mononuclear cells (MNC) by a semi-permeable membrane does not abrogate the inhibition of lymphocyte proliferation [20,24,25,26,27,28]
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