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Blood, 16 July 2009, Vol. 114, No. 3, pp. 693-701. Prepublished online as a Blood First Edition Paper on May 20, 2009; DOI 10.1182/blood-2009-03-213850. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-03-213850v1 114/3/693    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Highfill, S. L. Articles by Blazar, B. R. PubMed PubMed Citation Articles by Highfill, S. L. Articles by Blazar, B. R. Related Collections Hematopoiesis and Stem Cells Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Multipotent adult progenitor cells can suppress graft-versus-host disease via prostaglandin E2 synthesis and only if localized to sites of allopriming Steven L. Highfill1, Ryan M. Kelly1, Matthew J. O'Shaughnessy1, Qing Zhou1, Lily Xia1, Angela Panoskaltsis-Mortari1, Patricia A. Taylor1, Jakub Tolar1,*, and Bruce R. Blazar1,* 1 University of Minnesota Masonic Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, Minneapolis Multipotent adult progenitor cells (MAPCs) are nonhematopoietic stem cells capable of giving rise to a broad range of tissue cells. As such, MAPCs hold promise for tissue injury repair after transplant. In vitro, MAPCs potently suppressed allogeneic T-cell activation and proliferation in a dose-dependent, cell contact–independent, and T-regulatory cell–independent manner. Suppression occurred primarily through prostaglandin E2 synthesis in MAPCs, which resulted in decreased proinflammatory cytokine production. When given systemically, MAPCs did not home to sites of allopriming and did not suppress graft-versus-host disease (GVHD). To ensure that MAPCs would colocalize with donor T cells, MAPCs were injected directly into the spleen at bone marrow transplantation. MAPCs limited donor T-cell proliferation and GVHD-induced injury via prostaglandin E2 synthesis in vivo. Moreover, MAPCs altered the balance away from positive and toward inhibitory costimulatory pathway expression in splenic T cells and antigen-presenting cells. These findings are the first to describe the immunosuppressive capacity and mechanism of MAPC-induced suppression of T-cell alloresponses and illustrate the requirement for MAPC colocalization to sites of initial donor T-cell activation for GVHD inhibition. Such data have implications for the use of allogeneic MAPCs and possibly other immunomodulatory nonhematopoietic stem cells for preventing GVHD in the clinic. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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