Adipose Tissue-Derived Mesenchymal Stem Cells Have a Heterogenic Cytokine Secretion Profile

Abstract

Mesenchymal stem cells derived from adipose tissue (ASC) have immune regulatory function, which makes them interesting candidates for cellular therapy. ASC cultures are however heterogeneous in phenotype. It is unclear whether all ASC contribute equally to immunomodulatory processes. ASC are also responsive to cytokine stimulation, which may affect the ratio between more and less potent ASC populations. In the present study, we determined IL-6 receptor (CD126 and CD130 subunits) and IFN-γ receptor (CD119) expression on ASC by flow cytometry. The production of IL-6 and IFN-γ was measured by ELISA and the frequency of IL-6 and IFN-γ secreting cells by ELISPOT. The results showed that ASC did not express CD126, and only 10–20% of ASC expressed CD130 on their surface, whereas 18–31% of ASC expressed CD119. ASC produced high levels of IL-6 and 100% of ASC were capable of secreting IL-6. Stimulation by IFN-γ or TGF-β had no effect on IL-6 secretion by ASC. IFN-γ was produced by only 1.4% of ASC, and TGF-β significantly increased the frequency to 2.7%. These results demonstrate that ASC cultures are heterogeneous in their cytokine secretion and receptor expression profiles. This knowledge can be employed for selection of potent, cytokine-producing, or responsive ASC subsets for cellular immunotherapy.

Identifying the Therapeutic Significance of Mesenchymal Stem Cells

“…The mode of immunomodulation is mediated by cell-cell interactions, cytokines and soluble factors. Note that, depending on the levels of stimulation, MSCs play either pro-inflammatory or anti-inflammatory roles in its microenvironment (Figure 1) [13,15,24,25].…”

“…There are various sources of isolation of MSCs such as adipose tissue, bone marrow, peripheral blood and neonatal tissues (umbilical cord, placenta, amniotic fluid, and amniotic membrane) [2,[10][11][12]. The source of isolation of MSCs greatly affects the yield, the expressed variety of surface markers and cytokine profile [13][14][15]. However, the basic identification markers of MSCs are CD73 (cluster of differentiation 73), CD105, CD90 but they should be CD34-, CD14-, CD45-, CD11b-, CD19-and lack HLAII (Human Leukocyte Antigen complex 2) [16].…”

Cryopreservation Impacts Cell Functionality of Long Term Expanded Adipose-Derived Stem Cells

“…There is also evidence that perpetual inflammation associated with chronic inflammatory diseases resulted on permanent stimulation of TLR by their ligands continuously present within the inflamed environment, leading to up-regulation of IL-6 release [21]. Adding to that, ADSC might be auto-induced by Tumor Growth Factor-β (TGF-β), TLR2, TNF-αresulting in different inflammatory factors secretion panel as already reported [16,[47][48][49]. In serum-free conditions, ADSC also secreted IL-6, IL-10, and TGF-β [44].…”

Self-Organized Liver Microtissue on a Bio-Functional Surface: The Role of Human Adipose-Derived Stromal Cells in Hepatic Function

“…hASCs secrete various factors that regulate the cellular activity of neighboring cells, such as cell proliferation and differentiation [ 39 , 40 , 41 ]. To investigate whether changes in liver-specific gene expression in hASC-miHep co-spheroids were due to factors secreted from hASCs, mature miHeps were cultured with the CM of hASCs cultured in 2D or 3D ( Figure 4 A).…”