Immunosuppressive properties of Wharton’s jelly-derived mesenchymal stromal cells in vitro

Abstract

Recent studies have reported that mesenchymal stromal cells (MSCs) migrate to areas of inflammation and suppress adverse immune reactions. Bone marrow (BM)-derived MSCs have been successfully used in patients with acute graft versus host disease (GVHD), but the harvesting of BM carries certain risks for the donor. To circumvent these, we obtained MSCs from Wharton's jelly (WJ) derived from umbilical cord and investigated their potential for immunosuppression. In a mixed lymphocyte reaction (MLR), responder T cell proliferation triggered by allogeneic dendritic cells was inhibited efficiently by WJ-MSCs derived from the same donor of responder cells or those from a third party donor. These inhibitory effects were reversed in a dose-dependent manner in the presence of 1-methyl-DL-tryptophan, an inhibitor of the soluble factor indoleamine 2, 3-dioxygenase (IDO). Immunosuppression by WJ-MSCs was also attenuated by blocking cell-cell contact between WJ-MSCs and responder T cells using a Transwell chamber. Moreover, IDO gene expression was induced in both WJ- and BM-MSCs by inflammatory cytokine IFN-γ, but HLA-DR was expressed in BM-MSCs and not in WJ-MSCs upon stimulation by a relatively low concentration of IFN-γ. These results indicate that WJ-MSCs exert their immunosuppressive effects by cell-cell contact with activated T cells and in part through IDO, and suggest the need for cells rather than soluble factors secreted from MSCs to achieve immunosuppressive therapy in severe cases of GVHD.

Locally Delivered Umbilical Cord Mesenchymal Stromal Cells Reduce Chronic Inflammation in Long-Term Nonhealing Wounds: A Randomized Study

“…The effectiveness of UCMSC therapy can also be explained by their immunomodulatory properties. In vitro experiments have shown that UCMSCs, as well as MSCs isolated from bone marrow and adipose tissue, possess the ability to reduce the expression of proinflammatory cytokines by immune cells [47][48][49] and to inhibit the proliferation of activated T lymphocytes [50][51][52]. They also suppress the differentiation and maturation of dendritic cells [53,54] and mediate the induction of a regulatory phenotype in activated T lymphocytes (Treg) [55,56].…”

The rationale of using mesenchymal stem cells in patients with COVID-19-related acute respiratory distress syndrome: What to expect

“…However, an explant culture system provides a more physiologic milieu to harvest intact cells compared with enzymatic isolation. 51 UC-MSCs are positive for CD73, CD90, CD105, and human leukocyte antigen (HLA) class I and negative for CD45 and HLA-DR. 36,52 They display immunosuppressive potential by cell-cell contact with activated T cells, 53 and they efficiently suppress the proliferation and cytokine production of a subset of circulating T cells. 54 Moreover, UC-MSCs produce large amounts of tolerogenic IL-6, transforming growth factor (TGF)-β, and VEGF-1.…”

Effect of culture environement on mesenchymal stem cell immunomodulatory ability

“…Absence of signifi cant stimulation of allogeneic lymphocytes by different type of MSCs has been documented [6]. MSC from different sources; Bone Marrow (BM) [7], Placenta (PL-MSC) [8], Umbilical Cord (UC-MSC) [6], Wharton's Jelly (WJ-MSC) [9], Umbilical Cord Lining (CL-MSCs) and Cord Blood (CB-MSCs) [10], Amniotic Membrane (AM-MSC) [6,11], tonsil [12], cornea [13] and Liver [14], Adipose Tissue (AT-MSC) [15], exert their immunomodulatory effect on immune cells. This could confi rm the universal inhibitory effect of MSCs despite their origins or culture environment.…”