PMID- 20386557 OWN - NLM STAT- MEDLINE DCOM- 20110614 LR - 20181201 IS - 1440-1711 (Electronic) IS - 0818-9641 (Linking) VI - 88 IP - 8 DP - 2010 Nov-Dec TI - Immunosuppressive properties of human umbilical cord-derived mesenchymal stem cells: role of B7-H1 and IDO. PG - 795-806 LID - 10.1038/icb.2010.47 [doi] AB - 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-gamma (IFN-gamma) treatment. In addition, IFN-gamma treatment induced indoleamine 2,3-dioxygenase (IDO) and HLA-DR expression in UCMSCs. Neither control nor IFN-gamma-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. FAU - Tipnis, Shabari AU - Tipnis S AD - Regenerative Medicine, Reliance Life Sciences Pvt Ltd, Dhirubhai Ambani Life Sciences Centre, Navi Mumbai, Maharashtra, India. FAU - Viswanathan, Chandra AU - Viswanathan C FAU - Majumdar, Anish S AU - Majumdar AS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100413 PL - United States TA - Immunol Cell Biol JT - Immunology and cell biology JID - 8706300 RN - 0 (Antibodies, Blocking) RN - 0 (Antigens, CD) RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (HLA-DR Antigens) RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) RN - 82115-62-6 (Interferon-gamma) RN - 8DUH1N11BX (Tryptophan) SB - IM MH - Antibodies, Blocking/pharmacology MH - Antigens, CD/immunology/*metabolism MH - B7-H1 Antigen MH - Cell Communication/immunology MH - Cell Differentiation/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Dendritic Cells/metabolism/pathology MH - Fetal Blood/cytology MH - HLA-DR Antigens/genetics/metabolism MH - Humans MH - Immune Tolerance/drug effects MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism MH - Interferon-gamma/immunology/metabolism MH - Lymphocyte Activation MH - Lymphocyte Culture Test, Mixed MH - Mesenchymal Stem Cells/cytology/drug effects/immunology/*metabolism MH - T-Lymphocytes, Regulatory/metabolism/pathology MH - Tryptophan/analogs & derivatives/pharmacology EDAT- 2010/04/14 06:00 MHDA- 2011/06/15 06:00 CRDT- 2010/04/14 06:00 PHST- 2010/04/14 06:00 [entrez] PHST- 2010/04/14 06:00 [pubmed] PHST- 2011/06/15 06:00 [medline] AID - icb201047 [pii] AID - 10.1038/icb.2010.47 [doi] PST - ppublish SO - Immunol Cell Biol. 2010 Nov-Dec;88(8):795-806. doi: 10.1038/icb.2010.47. Epub 2010 Apr 13.