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

Abstract

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. 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. 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. 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.