title: Recruitment by SDF-1α of CD34-positive cells involved in sciatic nerve regeneration.
abstract: OBJECTIVE
  Increased integration of CD34(+) cells in injured nerve significantly promotes nerve regeneration, but this effect can be counteracted by limited migration and short survival of CD34(+) cells. SDF-1α and its receptor mediate the recruitment of CD34(+) cells involved in the repair mechanism of several neurological diseases. In this study, the authors investigate the potentiation of CD34(+) cell recruitment triggered by SDF-1α and the involvement of CD34(+) cells in peripheral nerve regeneration.
  
  
  METHODS
  Peripheral nerve injury was induced in 147 Sprague-Dawley rats by crushing the left sciatic nerve with a vessel clamp. The animals were allocated to 3 groups: Group 1, crush injury (controls); Group 2, crush injury and local application of SDF-1α recombinant proteins; and Group 3, crush injury and local application of SDF-1α antibody. Electrophysiological studies and assessment of regeneration markers were conducted at 4 weeks after injury; neurobehavioral studies were conducted at 1, 2, 3, and 4 weeks after injury. The expression of SDF-1α, accumulation of CD34(+) cells, immune cells, and angiogenesis factors in injured nerves were evaluated at 1, 3, 7, 10, 14, 21, and 28 days after injury.
  
  
  RESULTS
  Application of SDF-1α increased the migration of CD34(+) cells in vitro, and this effect was dose dependent. Crush injury induced the expression of SDF-1α, with a peak of 10-14 days postinjury, and this increased expression of SDF-1α paralleled the deposition of CD34(+) cells, expression of VEGF, and expression of neurofilament. These effects were further enhanced by the administration of SDF-1α recombinant protein and abolished by administration of SDF-1α antibody. Furthermore, these effects were consistent with improvement in measures of neurological function such as sciatic function index, electrophysiological parameters, muscle weight, and myelination of regenerative nerve.
  
  
  CONCLUSIONS
  Expression of SDF-1α facilitates recruitment of CD34(+) cells in peripheral nerve injury. The increased deposition of CD34(+) cells paralleled significant expression of angiogenesis factors and was consistent with improvement of neurological function. Utilization of SDF-1α for enhancing the recruitment of CD34(+) cells involved in peripheral nerve regeneration may be considered as an alternative treatment strategy in peripheral nerve disorders.
authors.affiliation: Institutes of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Meei-Ling
authors.initials: ML
authors.lastname: Sheu
authors.forename: Fu-Chou
authors.initials: FC
authors.lastname: Cheng
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Su
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Chiang
authors.forename: Wen-Ta
authors.initials: WT
authors.lastname: Chiu
authors.forename: Jason
authors.initials: J
authors.lastname: Sheehan
authors.forename: Hung-Chuan
authors.initials: HC
authors.lastname: Pan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D018952:Antigens, CD34; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat