Document Detail


Secretion of SDF-1alpha by bone marrow-derived stromal cells enhances skin wound healing of C57BL/6 mice exposed to ionizing radiation.
MedLine Citation:
PMID:  19725920     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients treated for cancer therapy using ionizing radiation (IR) have delayed tissue repair and regeneration. The mechanisms mediating these defects remain largely unknown at present, thus limiting the development of therapeutic approaches. Using a wound healing model, we here investigate the mechanisms by which IR exposure limits skin regeneration. Our data show that induction of the stromal cell-derived growth factor 1alpha (SDF-1alpha) is severely impaired in the wounded skin of irradiated, compared to non-irradiated, mice. Hence, we evaluated the potential of bone marrow-derived multipotent stromal cells (MSCs), which secrete high levels of SDF-1alpha, to improve skin regeneration in irradiated mice. Injection of MSCs into the wound margin led to remarkable enhancement of skin healing in mice exposed to IR. Injection of irradiated MSCs into the wound periphery of non-irradiated mice delayed wound closure, also suggesting an important role for the stromal microenvironment in skin repair. The beneficial actions of MSCs were mainly paracrine, as the cells did not differentiate into keratinocytes. Specific knockdown of SDF-1alpha expression led to drastically reduced efficiency of MSCs in improving wound closure, indicating that SDF-1alpha secretion by MSCs is largely responsible for their beneficial action. We also found that one mechanism by which SDF-1alpha enhances wound closure likely involves increased skin vascularization. Our findings collectively indicate that SDF-1alpha is an important deregulated cytokine in irradiated wounded skin, and that the decline in tissue regeneration potential following IR can be reversed, given adequate microenvironmental support.
Authors:
Yannick Landry; Oanh Lê; Kimberly A Mace; Terry E Restivo; Christian M Beauséjour
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-01
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  14     ISSN:  1582-4934     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-07-30     Completed Date:  2010-11-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  1594-604     Citation Subset:  IM    
Affiliation:
CHU Ste-Justine and Département de pharmacologie, Université de Montréal, Montréal, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells / cytology*
Chemokine CXCL12 / secretion*
Female
Mice
Mice, Inbred C57BL
Multipotent Stem Cells / cytology,  secretion,  transplantation
Neovascularization, Physiologic / radiation effects
Radiation, Ionizing
Skin / pathology*,  radiation effects*
Stromal Cells / radiation effects,  secretion,  transplantation
Time Factors
Wound Healing / radiation effects*
Grant Support
ID/Acronym/Agency:
MOP-79317//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Chemokine CXCL12

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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