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

Meei Ling Sheu, Fu Chou Cheng, Hong Lin Su, Ying Ju Chen, Chun Jung Chen, Chih Ming Chiang, Wen Ta Chiu, Jason Sheehan, Hung Chuan Pan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)432-444
Number of pages13
JournalJournal of Neurosurgery
Volume116
Issue number2
DOIs
Publication statusPublished - Feb 2012

Keywords

  • Hematopoietic progenitor cell
  • Nerve regeneration
  • Peripheral nerve
  • Sciatic nerve crush injury
  • SDF-1α

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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    Sheu, M. L., Cheng, F. C., Su, H. L., Chen, Y. J., Chen, C. J., Chiang, C. M., Chiu, W. T., Sheehan, J., & Pan, H. C. (2012). Recruitment by SDF-1α of CD34-positive cells involved in sciatic nerve regeneration: Laboratory investigation. Journal of Neurosurgery, 116(2), 432-444. https://doi.org/10.3171/2011.3.JNS101582