Abstract C38: Immunosuppression by indoleamine 2,3-dioxygenase in mesenchymal stem cells derived from adult human tissues

• Published in: Molecular cancer therapeutics Vol. 8; no. 12_Supplement; p. C38
• Main Authors: Lee, Myoung Woo, Jang, In Keun, Noh, Yoo Hun, Kim, Dae Seong, Kim, Hye Ryung, Cheuh, Hee Won, Lee, Soo Hyun, Jung, Hye Lim, Sung, Ki Woong, Koo, Hong Hoe
• Format: Journal Article
• Language: English
• Published: 10.12.2009
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.TARG-09-C38

Abstract Mesenchymal stem cells (MSCs), which evoke only minimal immune reactivity, may have anti-inflammatory and immunomodulatory effects. In this study, we conducted a comparative analysis of the immunomodulatory properties of MSCs derived from adult human tissues including bone marrow (BM), adipose tissues (AT), umbilical cord blood (CB), and cord Wharton's jelly (WJ). Using a multiple cytokine detection assay, we showed that there were no significant differences in levels of secreted factors from non-stimulated MSCs. We compared the immunosuppressive effect of BM-MSCs, AT-MSCs, CB-MSCs, and WJ-MSCs on phytohemagglutinin (PHA)-induced T-cell proliferation. AT-MSCs, CB-MSCs, and WJ-MSCs effectively suppressed PHA-induced T-cell proliferation as effectively as did BM-MSCs. Levels of interferon (IFN)-γ secreted from activated T-cells increased over time, but these levels were significantly reduced when cocultured with each type of MSCs. In addition, the expression of hepatocyte growth factor, interleukin-10, transforming growth factor-β1, cyclooxygenase (COX)-1, and COX-2 were unchanged in MSCs treated with IFN-γ, while that of indoleamine 2,3-dioxygenase (IDO) increased. Use of an antagonist, 1-methyl-L-tryptophan, restored T-cell proliferation and confirmed an IDO contribution to IFN-γ-induced immunosuppression by MSCs. Addition of tryptophan catabolite, such as kynurenine, 3-hydroxykynurenine, or quinolinic acid, significantly decreased PHA-induced T-cell proliferation. These data indicate that IFN-γ produced by activated T-cells were correlated with induction of IDO expression by MSCs, which, in turn, suppressed T-cell proliferation through tryptophan depletion and the local accumulation of tryptophan catabolites. Our findings suggest that MSCs derived from AT, CB, or WJ could be substituted for BM-MSCs for treatment of allogeneic conflicts. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C38.