Immunomodulatory capacity of human mesenchymal stem cells isolated from adipose tissue, dental pulp, peripheral blood and umbilical cord Wharton's jelly

Abstract

Mesenchymal stem cells (MSCs), beside regenerative potential, possess immunomodulatory properties and their use in managing immune-mediated diseases is intensively studied. We analyzed the effects of MSCs isolated from human adipose tissue (AT-MSCs), dental pulp (DP-MSCs), peripheral blood (PB-MSCs) and umbilical cord Wharton's jelly (UC-MSCs), on the proliferation of allogeneic peripheral blood mononuclear cells (PBMCs). While only AT-MSCs functioned as alloantigen presenting cells, proliferation of PBMCs in response to a phytohemagglutinin (PHA) and alloantigens in mixed lymphocytes reaction (MLR) was inhibited by all MSCs in a cell concentration-dependent manner. Conditioned medium (CM) derived from DP-MSCs, PB-MSCs and UC-MSCs, suppressed the baseline, PHA- and alloantigens-mediated proliferation of PBMC, whereas AT-MSCs-derived CM inhibited MLR, but failed to suppress the spontaneous and PHA-induced PBMCs proliferation. Differences between MSC types were observed in expression of genes related to immunomodulation, including human leukocyte antigens (HLA)-A, HLA-DR, HLA-G5, interleukin 6 (IL)-6, transforming growth factor (TGF)-beta, cyclooxygenase-2 (COX-2) and indoleamine 2,3-dioxygenase (IDO-1), under basal conditions, as well as in response to proinflammatory cytokines, interferon (IFN)-gamma and tumor necrosis factor alpha (TNF)-alpha. While AT-MSCs showed a positive constitutive expression of almost all tested genes that was augmented in response to IFN-gamma and TNF-alpha, only combined cytokine treatment increased HLA-A, COX2 and IL-6 mRNA expression in DP-MSCs and slightly stimulated the expression of HLA-G and TGF-beta in UC-MSCs. Although MSCs from different tissues showed similar potential to suppress proliferation of PBMCs, heterogeneity in the expression of genes related to immunomodulation emphasizes the importance of investigating the role of specific molecular mechanisms in the regulation of immunomodulatory activity of MSCs.