The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor.

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be corroborated in humans.

Accumulation of soluble inflammatory mediators between blood donation and pre-storage leucocyte depletion.

BACKGROUND AND OBJECTIVES: Leucocyte-derived cytokines accumulate in stored whole blood. Pre-storage leucocyte depletion has reduced cytokine levels and, consequently, febrile non-haemolytic transfusion reactions. As leucocyte filtration and component separation can be performed until 24 h after donation, we hypothesized that within this time, inflammatory cytokines might accumulate. MATERIALS AND METHODS: Serial plasma samples were collected 4, 10 and 20 h after donation and cytokine concentrations were measured. RESULTS: Interleukin-8 increased > 20-fold and soluble CD40 ligand > sixfold during the observation time, less pronounced changes for several other mediators were also observed. CONCLUSION: Leucocyte depletion within 10 h of blood donation will reduce the concentrations of pyrogenic mediators.