IL-17 mobilizes peripheral blood stem cells with short- and long-term repopulating ability in mice

Autologous and allogeneic bone marrow transplantations have evolved as impo rtant cancer therapy modalities. For both indications, peripheral blood has been shown to have distinct advantages over bone marrow as the stem cell s ource. Cytokine combinations for mobilization have enhanced stem cell yield and accelerated engraftment. However, novel mobilizing agents and strategi es are needed to further improve clinical outcomes. Within the donor graft, the dynamic equilibrium between T cells and stem cells critically influenc es engraftment and transplantation results. IL-17 is a cytokine produced al most exclusively from activated T cells. IL-17 was expressed in vivo with a denovirus technology. Here, proof-of-principle studies demonstrate that IL- 17 effectively mobilizes hemopoietic precursor cells (CFU-granulocyte-eryth rocyte-macrophage-monocyte, CFU-high proliferative potential) and primitive hemopoietic stem cells (Lin(-/low)c-kit(+)Sca1(+)). Moreover, mouse IL-17 adenovirus-mobilized peripheral blood stem cells rescued lethally irradiate d mice. Bone marrow was found to be 45-75% of donor origin at I year. In se condary recipients, donor-derived bone marrow cells ranged from 45 to 95%. These data show that IL-17 mobilizes stem cells in mice with short- and lon g-term reconstituting capacity. Additional comparative studies are needed a s well as studies in tumor models to refine distinct potential clinical app lications for IL-17-mobilized peripheral blood stem cells.