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IL-17 Mobilizes Peripheral Blood Stem Cells with Short- and Long-Term Repopulating Ability in Mice¹

Paul Schwarzenberger^2,*,, Weitao Huang^*,, Peter Oliver^*,, Patrick Byrne^*,, Vincent La Russa, Zili Zhang^*, and Jay K. Kolls^*,,

^* Gene Therapy Program, and Departments of Medicine and Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA 70112; and Bone Marrow Transplantation Program, Tulane University, New Orleans, LA 70118

Autologous and allogeneic bone marrow transplantations have evolved as important cancer therapy modalities. For both indications, peripheral blood has been shown to have distinct advantages over bone marrow as the stem cell source. Cytokine combinations for mobilization have enhanced stem cell yield and accelerated engraftment. However, novel mobilizing agents and strategies are needed to further improve clinical outcomes. Within the donor graft, the dynamic equilibrium between T cells and stem cells critically influences engraftment and transplantation results. IL-17 is a cytokine produced almost exclusively from activated T cells. IL-17 was expressed in vivo with adenovirus technology. Here, proof-of-principle studies demonstrate that IL-17 effectively mobilizes hemopoietic precursor cells (CFU-granulocyte-erythrocyte-macrophage-monocyte, CFU-high proliferative potential) and primitive hemopoietic stem cells (Lin^-/lowc-kit⁺Sca1⁺). Moreover, mouse IL-17 adenovirus-mobilized peripheral blood stem cells rescued lethally irradiated mice. Bone marrow was found to be 45–75% of donor origin at 1 year. In secondary 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 long-term reconstituting capacity. Additional comparative studies are needed as well as studies in tumor models to refine distinct potential clinical applications for IL-17-mobilized peripheral blood stem cells.

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