Secretion of Indoleamine 2,3-Dioxygenase, an Immunomodulatory Substance, by Adipose-Derived Mesenchymal Stem Cell
Abstract
Lipoaspirate, a wasted by product from liposuction procedure recently has been shown to contain abundant adipose-derived-mesenchymal stem cells (MSCs). Mesenchymal stem cells (MSCs) have been studied in many research areas to regenerate many cell lineages. In addition, MSCs have immunomodulatory effect. This capability has been utilized in several clinical studies in hematopoetic stem cell and organ transplantation as a strategy to reduce the risk of Graft versus Host Disease (GvHD). It has been reported that the ‘stimulated’ MSC is able to secrete substances to suppress tissue rejection. One of the substances was known to be indoleamine 2,3-dioxygenase (IDO). A previous study has characterized the secretion of IDO by bone marrow-derived MSCs stimulated by an inflammatory mediator interferon gamma (IFN-γ). IDO has been detected using Western blot analysis and by High Performance Liquid Chromatography (HPLC) assay. The aim of this study was to detect the presence of IDO in AD-MSCs culture with and without INFγ stimulation. Our study showed that AD-MSC stimulated with IFN-γ significantly secreted high level of IDO as detected by Enzyme-Linked Immuno Sorbent Assay (ELISA). Despite its property as a proinflammatory mediator, IFN-γ has shown to be able to induce IDO secretion in MSC culture which suggests the immuno modulatory effect of MSC. This study clearly demonstrates the potential application of adipose-derived MSC in the immunomodulatory strategy for allogenic transplantation.
Keyword : mesenchymal stem cell, indoleamine 2,3-dioxygenase, IFN-γ
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Aggarwal, S., and M.F. Pittenger. 2005. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4):1815-1822.
DelaRosa, O., E. Lombardo, A. Beraza, P. Mancheno-Corvo, C. Ramirez, R. Menta, L. Rico, E. Camarillo, L. Garcia, J.L. Abad, C. Trigueros, M. Delgado, and D. Buscher. 2009. Requirement of IFN-gamma-mediated indoleamine 2,3-dioxygenase expression in the modulation of lymphocyte proliferation by human adipose-derived stem cells. Tissue Eng Part A 15(10):2795-2806.
Di Nicola, M., C. Carlo-Stella, M. Magni, M. Milanesi, P.D. Longoni, P. Matteucci, S. Grisanti, and A.M. Gianni. 2002. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99(10):3838-3843.
Dominici, M., K. Le Blanc, I. Mueller, I. Slaper-Cortenbach, F. Marini, D. Krause, R. Deans, A. Keating, D. Prockop, and E. Horwitz. 2006. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315-317.
Le Blanc, K. 2006. Mesenchymal stromal cells: Tissue repair and immune modulation. Cytotherapy 8(6):559-561.
Le Blanc, K., I. Rasmusson, B. Sundberg, C. Gotherstrom, M. Hassan, M. Uzunel, and O. Ringden. 2004. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363(9419):1439-1441.
Le Blanc, K., and O. Ringden. 2007. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 262(5):509-525.
Meisel, R., A. Zibert, M. Laryea, U. Gobel, W. Daubener, and D. Dilloo. 2004. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 103(12):4619-4621.
Mellor, A.L., and D.H. Munn. 2004. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4(10):762-774.
Munn, D.H., and A.L. Mellor. 2007. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest 117(5):1147-1154.
Puissant, B., C. Barreau, P. Bourin, C. Clavel, J. Corre, C. Bousquet, C. Taureau, B. Cousin, M. Abbal, P. Laharrague, L. Penicaud, L. Casteilla, and A. Blancher. 2005. Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol 129(1):118-129.
Sanchez-Ramos, J., S. Song, F. Cardozo-Pelaez, C. Hazzi, T. Stedeford, A. Willing, T.B. Freeman, S. Saporta, W. Janssen, N. Patel, D.R. Cooper, and P.R. Sanberg. 2000. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164(2):247-256.
Sardjono, C., M. Setiawan, Frisca, V. Saputra, G. Aniko, and F. Sandra. 2009. Application of a modified method for stem cell isolation from lipoaspirates in a basic lab. Medical Journal of Indonesia 18(2):91-96.
Sato, K., K. Ozaki, I. Oh, A. Meguro, K. Hatanaka, T. Nagai, K. Muroi, and K. Ozawa. 2007. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 109:228-234.
Schwartz, R.E., M. Reyes, L. Koodie, Y. Jiang, M. Blackstad, T. Lund, T. Lenvik, S. Johnson, W.S. Hu, and C.M. Verfaillie. 2002. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 109:1291-1302.
Suzuki, S., S. Tone, O. Takikawa, T. Kubo, I. Kohno, and Y. Minatogawa. 2001. Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early concepti. Biochem J 355(Pt 2):425-429.
Suzuki, T., K. Yokouchi, H. Kawamichi, Y. Yamamoto, K. Uda, and H.J. Yuasa. 2003. Comparison of the sequences of Turbo and Sulculus indoleamine dioxygenase-like myoglobin genes. Gene 308:89-94.
Yanez, R., M.L. Lamana, J. Garcia-Castro, I. Colmenero, M. Ramirez, and J.A. Bueren. 2006. Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells 24:2582-2591.
Zhang, R.L., E.L. Jiang, M. Wang, Z. Zhou, W.J. Zhai, W.H. Zhai, H. Wang, Z.Y. Wang, Y.S. Bao, H. Du, and M.Z. Han. 2008. [Differentiation of bone marrow derived from mesenchymal stem cells into cardiomyocyte-like cells induced by co-culture with rat myocardial cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 16:1111-1115.
DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev1iss2pp92-98
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