title: A soluble granulocyte colony stimulating factor decoy receptor as a novel tool to increase hematopoietic cell homing and reconstitution in mice.
abstract: The relative ineffectiveness of hematopoietic stem cells in reaching the bone marrow upon transplantation combined with the limited number of these cells available is a major reason for graft failure and delayed hematopoietic recovery. Hence, the development of strategies that could enhance homing is of high interest. Here, we provide evidence that homing is severely impaired postexposure to ionizing radiation (IR) in mice, an effect we found was time dependent and could be partially rescued using mesenchymal stromal cell (MSC) therapy. In an attempt to further increase homing, we took advantage of our observation that the granulocyte colony stimulating factor (G-CSF), a cytokine known to induce cell mobilization, is increased in the marrow of mice shortly after their exposure to IR. As such, we developed a truncated, yet functional, soluble G-CSF receptor (solG-CSFR), which we hypothesized could act as a decoy and foster homing. Using MSCs or conditioned media as delivery vehicles, we show that an engineered solG-CSFR has the potential to increase homing and hematopoietic reconstitution in mice. Altogether, our results provide novel findings at the interplay of IR and stromal cell therapy and present the regulation of endogenous G-CSF as an innovative proof-of-concept strategy to manipulate hematopoietic cell homing.
authors.affiliation: Centre de recherche du CHU Ste-Justine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Fortin
authors.forename: Basma
authors.initials: B
authors.lastname: Benabdallah
authors.forename: Lina
authors.initials: L
authors.lastname: Palacio
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Carbonneau
authors.forename: Oanh N
authors.initials: ON
authors.lastname: Le
authors.forename: Elie
authors.initials: E
authors.lastname: Haddad
authors.forename: Christian M
authors.initials: CM
authors.lastname: Beauséjour
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects*; D002478:Cells, Cultured; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D012995:Solubility
chemical_list: D010446:Peptide Fragments; D016188:Receptors, Granulocyte Colony-Stimulating Factor