title: CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair.
abstract: BACKGROUND
  Bone marrow-derived mesenchymal stem cells (BM-MSCs) play a crucial role in tissue repair. Their role in thermal burn wound regeneration and the relevant mechanism, however, is rarely studied.
  
  
  METHODS
  BM-MSCs from green fluorescent protein transgenic male mice were transfused to irradiated recipient female C57BL/6 mice. Twenty-one days later, the female mice were inflicted with burn wounds. The size of the burned area was measured by an in vivo fluorescence imaging system, and BM-MSC chemotaxis and epithelialization were estimated by fluorescence in situ hybridization and immunofluorescence technology. The expression of CXCL12 and CXCR4 in the wound margin was detected by enzyme-linked immunosorbent assay and immunohistochemistry. The importance of CXCL12/CXCR4 signaling in BM-MSC chemotaxis was further estimated by blocking CXCR4 in vivo and in vitro.
  
  
  RESULTS
  In vivo imaging results showed that BM-MSCs migrated to the injured margins. Fluorescence in situ hybridization and immunofluorescence technology revealed that Y chromosome-positive cells derived from green fluorescent protein transgenic mice were detected to be colocalized with keratin protein. Enzyme-linked immunosorbent assay revealed increased levels of CXCL12 and CXCR4 protein in the wound sites of BM-MSC-treated chimeric mice after burn. Immunohistochemistry also disclosed that CXCL12 levels were elevated at postburn day 7 compared with day 0. Furthermore, pretreatment of the BM-MSCs with the CXCR4 antagonist AMD3100 significantly inhibited the mobilization of BM-MSCs in vitro and in vivo, which attenuated wound closure.
  
  
  CONCLUSIONS
  BM-MSC migration to the burned margins promotes the epithelialization of the wound, and mobilization of BM-MSCs is mediated by CXCL12/CXCR4 signaling.
authors: Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors: Changjiang
authors: C
authors: Hu
authors: Xin
authors: X
authors: Yong
authors: Changzhu
authors: C
authors: Li
authors: Muhan
authors: M
authors: Lü
authors: Dengqun
authors: D
authors: Liu
authors: Lin
authors: L
authors: Chen
authors: Jiongyu
authors: J
authors: Hu
authors: Miao
authors: M
authors: Teng
authors: Dongxia
authors: D
authors: Zhang
authors: Yahan
authors: Y
authors: Fan
authors: Guangping
authors: G
authors: Liang
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis; D002678:Chimera; D000078404:Epidermal Cells; D005260:Female; D049452:Green Fluorescent Proteins; D018859:Hair Follicle / Q000166:cytology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D062326:Re-Epithelialization; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins