Document Detail


A soluble granulocyte colony stimulating factor decoy receptor as a novel tool to increase hematopoietic cell homing and reconstitution in mice.
MedLine Citation:
PMID:  23205715     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Audrey Fortin; Basma Benabdallah; Lina Palacio; Cynthia L Carbonneau; Oanh N Le; Elie Haddad; Christian M Beauséjour
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-11
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-01     Completed Date:  2013-08-12     Revised Date:  2014-03-26    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  975-84     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow / radiation effects
Cell Movement / radiation effects*
Cells, Cultured
Female
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells / physiology
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells / metabolism,  secretion
Mice
Mice, Inbred C57BL
Peptide Fragments / biosynthesis*,  genetics,  secretion
Receptors, Granulocyte Colony-Stimulating Factor / biosynthesis*,  genetics
Solubility
Grant Support
ID/Acronym/Agency:
MOP-102709//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/Receptors, Granulocyte Colony-Stimulating Factor
Comments/Corrections

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