Recruitment by SDF-1α of CD34-positive cells involved in sciatic nerve regeneration

Laboratory investigation

Meei-Ling Sheu Ph.D. 1 , Fu-Chou Cheng Ph.D. 6 , 4 , Hong-Lin Su Ph.D. 2 , Ying-Ju Chen Ph.D. 4 , Chun-Jung Chen Ph.D. 6 , Chih-Ming Chiang M.S. 5 , Wen-Ta Chiu M.D., Ph.D. 7 , Jason Sheehan M.D., Ph.D. 8 and Hung-Chuan Pan M.D., Ph.D. 1 , 3
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  • 1 Institutes of Biomedical Sciences and
  • 2 Life Sciences, National Chung-Hsing University;
  • 3 Departments of Neurosurgery,
  • 5 Radiology, and
  • 6 Education and Medical Research, and
  • 4 Stem Cell Center, Taichung Veterans General Hospital, Taichung;
  • 7 Department of Neurosurgery, Taipei Medical University–Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; and
  • 8 Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia
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Object

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.

Abbreviations used in this paper: CMAP = compound muscle action potential; ECM = extracellular matrix; G-CSF = granulocyte colony-stimulating factor; HPC = hematopoietic progenitor cell; RI = regularity index; SFI = sciatic function index.

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Contributor Notes

Address correspondence to: Hung-Chuan Pan, M.D., Ph.D., Department of Neurosurgery, Taichung Veterans General Hospital, No. 160, Taichung-Kang Road, Section 3, Taichung 407, Taiwan. email: hcpan2003@yahoo.com.tw.

Please include this information when citing this paper: published online August 19, 2011; DOI: 10.3171/2011.3.JNS101582.

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