| Immunosuppressive properties of human umbilical cord-derived mesenchymal stem cells: role of B7-H1 and IDO. | |
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MedLine Citation:
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PMID: 20386557 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Umbilical cord is a rich source of mesenchymal stromal or stem cells (MSCs) that can be used for developing allogeneic cell therapy to treat intractable diseases. In this report, we present evidence that umbilical cord-derived MSCs (UCMSCs) possess important immunomodulatory properties that may enable them to survive in an allogeneic environment. UCMSCs do not express human leukocyte antigen (HLA)-DR and co-stimulatory molecules CD80 and CD86 that are required for T-cell activation. More importantly, UCMSCs constitutively express a negative regulator of T-cell activation, B7-H1, and its expression is increased after interferon-γ (IFN-γ) treatment. In addition, IFN-γ treatment induced indoleamine 2,3-dioxygenase (IDO) and HLA-DR expression in UCMSCs. Neither control nor IFN-γ-treated UCMSCs stimulated allogeneic T-cell proliferation, and both cell populations inhibited third-party dendritic cell (DC)-mediated allostimulatory activity. Addition of a B7-H1-specific blocking antibody or an IDO inhibitor, 1 methyl tryptophan (1-MT) abrogated the T-cell immunosuppressive activity of these cells. Furthermore, UCMSCs prevented the differentiation and maturation of peripheral blood monocyte-derived DCs, and augmented the generation of regulatory T cells (Tregs) in culture. The immunosuppressive effects of UCMSCs are largely mediated by cell-to-cell contact, although some inhibitory activity was observed with cell-free supernatant. Our study suggests that these immunomodulatory properties of UCMSCs could potentially improve the outcome of allogeneic stem cell therapy. |
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Authors:
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Shabari Tipnis; Chandra Viswanathan; Anish S Majumdar |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-13 |
Journal Detail:
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Title: Immunology and cell biology Volume: 88 ISSN: 1440-1711 ISO Abbreviation: Immunol. Cell Biol. Publication Date: 2010 Nov-Dec |
Date Detail:
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Created Date: 2010-11-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8706300 Medline TA: Immunol Cell Biol Country: England |
Other Details:
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Languages: eng Pagination: 795-806 Citation Subset: IM |
Affiliation:
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Regenerative Medicine, Reliance Life Sciences Pvt Ltd, Dhirubhai Ambani Life Sciences Centre, Navi Mumbai, Maharashtra, India. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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