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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1815-1822. Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-04-1559. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-04-1559v1 105/4/1815    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles via Google Scholar Google Scholar Articles by Aggarwal, S. Articles by Pittenger, M. F Search for Related Content PubMed PubMed Citation Articles by Aggarwal, S. Articles by Pittenger, M. F Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 26, 2004 Accepted September 26, 2004 Human mesenchymal stem cells modulate allogeneic immune cell responses Sudeepta Aggarwal and Mark F Pittenger* Osiris Therapeutics, Inc., Baltimore, MD, USA * Corresponding author; email: mpittenger{at}osiristx.com. Mesenchymal stem cells (MSCs) are multipotent cells found in several adult tissues. Transplanted allogeneic MSCs can be detected in recipients at extended time points, indicating a lack of immune recognition and clearance. As well, a role for bone-marrow derived MSCs in reducing the incidence and severity of graft versus host disease (GVHD) during allogeneic transplantation has recently been reported; however, the mechanisms remain to be investigated. We examined the immuno-modulatory functions of human MSCs (hMSCs) by co-culturing them with purified sub-populations of immune cells and report here that hMSCs altered the cytokine secretion profile of dendritic cells (DCs), naive and effector T cells (TH1 and TH2), and natural killer (NK) cells to induce a more anti-inflammatory or tolerant phenotype. Specifically, the hMSCs caused mature DC1 to decrease TNF- secretion and mature DC2 to increase IL-10 secretion; hMSCs caused TH1 cells to decrease IFN- and caused the TH2 cells to increase secretion of IL-4; hMSCs caused an increase in the proportion of regulatory T cells (TReg) present; and hMSCs decreased secretion of IFN- from the NK cells. Mechanistically, the hMSCs constitutively produced prostaglandin E2 (PGE2) in culture and inhibitors of PGE2 production mitigated hMSC-mediated immune modulation. This data offers insight into the interactions between allogeneic MSCs and immune cells and provides mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection and modulation of inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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