Human multipotent adult progenitor cells effectively reduce graft ‐vs‐host disease while preserving graft‐vs‐leukemia activity following experimental, allogeneic bone marrow transplantation

We examined whether the administration of human, bone marrow-derived, multi-potent, adult progenitor cells (MAPC) could regulate experimental GvHD. The immuno-regulatory capacity of MAPC cells was evaluatedin vivo using established murine GvHD models. Injection of MAPC cells on Day +1 (D1) and  + 4 (D4) significantly reduced T-cell expansion and the numbers of donor-derived, TNFα and IFNγ-producing, CD4+ and CD8+ cells by D10 compared to untreated controls. These findings were associated with reductions in serum levels of TNFα and IFNγ, intestinal and hepatic inflammation and syst emic GvHD as measured by survival and clinical score. Biodistribution studies showed that MAPC cells tracked from the lung and into the liver, spleen, and mesenteric nodes within 24 hours after injection. MAPC cells inhibited mouse T-cell proliferationin vitro and this effect was associated with reduced T-cell activation and inflammatory cytokine secretion and robust increases in the concentrations of PGE2 and TGF β. Indomethacin and E-prostanoid 2 (EP2) receptor antagonism both reversed while EP2 agonism restored MAPC-mediatedin vitro T-cell suppression, confirming the role for PGE2. Furthermore, cyclo-oxygenase inhibition following allo-BMT abrogated the protective effects of MAPC cells. Importantly, MAPC cells had no effect on the generation CTL activityin vitro, and the administration of MAPC cells in the setting of leukemic challenge resulted in superior leukemia-free survival. Colle...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research