Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells

Abstract

In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell–cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles. Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets. According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells. The phenotypic characterization of cytotoxic and helper T cells (activation and differentiation markers) together with functional assays (proliferation and IFN-γ production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-γ release on in vitro stimulated cells. In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases.

The secretome of mesenchymal stromal cells: Role of extracellular vesicles in immunomodulation

“…In contrast, when cultured with basic fibroblast growth factor ASC-EVs show a decreased expression of angiogenic factors and an up-regulation of an antiangiogenic miRNA result in a reduced angiogenesis both in vitro and in vivo [56]. Human ASCs -Anti-proliferative effects [69] Nucleic acid analysis revealed that MSC-EVs are selectively enriched of distinct classes of RNAs.…”

“…ASCs have immunomodulatory capacity similar to MSCs derived from bone marrow [70]. When stimulated T lymphocytes are cultured with different concentrations of EVs from ASCs, an anti-proliferative effect has been observed for both CD4 + and CD8 + cells [69]. Phenotype analysis of lymphocytes cultured with ASC-EVs shows a decrease of terminally differentiated effectormemory CD8+ (CD45RA+CCR7−) and CD4+ (CD45RA−CCR7−) T cells and an increase of the central CD4+ T memory cells (CD45RA−CCR7+).…”

“…EVs derived from an alternative source of MSCs, such as adipose tissue, have been also tested on T lymphocyte proliferation and activity [69]. ASCs have immunomodulatory capacity similar to MSCs derived from bone marrow [70].…”

The promising role for adipose-derived mesenchymal stem cells in tissue regeneration

“…Another group demonstrated a significant role for PGE2 in modulating T lymphocyte transcription factors and cytokines to underlie the immunosuppressive effects. Interestingly, exosomes of ASCs were shown to be sufficient in inducing suppressive effects on T cell activation, differentiation, proliferation, and IFN-γ secretion [57]. With regards to cytotoxic T lymphocytes, MSCs could suppress development of but not actual cell lysis by these cells [58].…”

The Main Molecules Involved in Human Mesenchymal Stem Cells Immunomodulation

“…These factors are released into exosomes (Figure 1), which are small membranous vesicles secreted by most cell types that participate in cell-cell communication [15]. There are no differences in terms of morphological features, isolation, and storage conditions between exosomes derived from MSCs and other sources [16].…”