title: Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice.
abstract: OBJECTIVE
  The use of mesenchymal stem cells (MSC) for cell therapy relies on the capacity of these cells to home and engraft long-term into the appropriate target tissue(s). Homing of MSC to bone marrow (BM) post-transplantation can occur, but does so with only poor efficiency. This study was designed to evaluate the role of the SDF-1/CXCR4 axis in the homing of Flk1+ MSC derived from human fetal BM.
  
  
  METHODS
  We investigated the expression of CXCR4 in Flk1+ MSC stimulated with a cytokine cocktail and explored their homing ability 24 hours after intravenous infusion into sublethally irradiated NOD/SCID mice. The peripheral blood was analyzed and human cells in recipients' BM were quantified from 2 to 6 months after transplantation.
  
  
  RESULTS
  We found that Flk1+ MSC harbored intracellular CXCR4 which can be rapidly induced to the cell surface within a few hours. Short-term (24 hours) stimulation with the cocktail of cytokines resulted in up-regulation of both cell surface and intracellular CXCR4, increasing in vitro migration capacity to SDF-1 and homing to the BM of irradiated NOD/SCID mice. Moreover, compared to non-treated cells, transplantation of cytokine-treated Flk1+ MSC resulted in faster hematologic recovery and higher levels of donor chimerism in BM. Neutralization of CXCR4 significantly reduced homing and engraftment of Flk1+ MSCs in murine BM.
  
  
  CONCLUSIONS
  These results suggest that the SDF-1/CXCR4 axis plays an important role in the regulation of motility of Flk1+ MSC. Increasing CXCR4 expression might be a potential strategy to improve engraftment of MSC in BM and accelerate the recovery of hematopoiesis.
authors.affiliation: Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Shi
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Bingzong
authors.initials: B
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Hairong
authors.initials: H
authors.lastname: Jia
authors.forename: Robert Chunhua
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002465:Cell Movement; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000235:genetics*; D014183:Transplantation, Heterologous
chemical_list: D016207:Cytokines; D019718:Receptors, CXCR4