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

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-1 alpha 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-1 alpha 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-1 alpha recombinant proteins; and Group 3, crush injury and local application of SDF-1 alpha 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-1 alpha, 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-1 alpha increased the migration of CD34(+) cells in vitro, and this effect was dose dependent. Crush injury induced the expression of SDF-1 alpha, with a peak of 10-14 days postinjury, and this increased expression of SDF-1 alpha paralleled the deposition of CD34(+) cells, expression of VEGF, and expression of neurofilament. These effects were further enhanced by the administration of SDF-1 alpha recombinant protein and abolished by administration of SDF-1 alpha 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-1 alpha 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-1 alpha for enhancing the recruitment of CD34(+) cells involved in peripheral nerve regeneration may be considered as an alternative treatment strategy in peripheral nerve disorders. (DOI: 10.3171/2011.3.JNS101582