Journal
BLOOD
Volume 114, Issue 3, Pages 693-701Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-03-213850
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Funding
- NIH [R01 AI34495, HL56067, HL49997]
- Children's Cancer Research Fund
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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 E-2 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 E-2 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. (Blood. 2009;114:693-701)
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