Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells

Crop, M. J. and Baan, C. C. and Korevaar, S. S. and IJzermans, J. N. M. and Pescatori, M. and Stubbs, A. P. and van IJcken, W. F. J. and Dahlke, M. H. and Eggenhofer, E. and Weimar, W. and Hoogduijn, M. J. (2010) Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 162 (3). pp. 474-486. ISSN 0009-9104,

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Abstract

P>There is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose tissue-derived mesenchymal stem cells (ASC) were cultured with alloactivated peripheral blood mononuclear cells (PBMC) (mixed lymphocyte reaction: MLR), with proinflammatory cytokines [interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6] or under control conditions, and their full genome expression and function examined. Proinflammatory cytokines mainly increased indoleamine-2,3-dioxygenase expression, whereas ASC cultured with MLR showed increased expression of COX-2, involved in prostaglandin E-2 production. Both conditions had a stimulatory, but differential, effect on the expression of proinflammatory cytokines and chemokines, while the expression of fibrotic factors was decreased only in response to proinflammatory cytokines. Functional analysis demonstrated that inflammatory conditions affected morphology and proliferation of ASC, while their differentiation capacity and production of trophic factors was unaffected. The immunosuppressive capacity of ASC was enhanced strongly under inflammatory conditions. In conclusion, ASC showed enhanced immunosuppressive capacity under inflammatory conditions, while their differentiation capacity was preserved. Therefore, in vitro preconditioning provides ASC with improved properties for immediate clinical immune therapy.

Item Type: Article
Uncontrolled Keywords: SOLID-ORGAN TRANSPLANTATION; SUPPRESS T-LYMPHOCYTE; FALSE DISCOVERY RATE; STROMAL CELLS; INTERFERON-GAMMA; HUMAN HEART; CORD BLOOD; INHIBIT; PROLIFERATION; IMMUNOSUPPRESSION; cytokines; gene array; immunosuppression; inflammation; mesenchymal stem cell; microarray; mixed lymphocyte reactions
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 Jul 2020 07:22
Last Modified: 06 Jul 2020 07:22
URI: https://pred.uni-regensburg.de/id/eprint/23778

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