Schwann cell migration through freeze-killed peripheral nerve grafts without accompanying axons

Summary Freeze-dried tibial nerve grafts were anastomosed to either the proximal stump or the distal stump of severed tibial nerves in adult inbred Fischer rats. In the case of grafts attached to the proximal stump the tibial nerve was ligated three times, the most distal ligature from the spinal cord being 1 cm from the site of anastomosis. In both types of experiment Schwann cells were, therefore, free to enter the initially acellular grafts without accompanying axons. The grafts were examined 17 days to 12 weeks after operation. Immunofluorescence for S-100 protein was used to evaluate the distance migrated by the Schwann cells and electron microscopy was used to examine the morphology of the cells which invaded the grafts. Schwann cell migration was similar from the proximal and distal stumps. The migrating Schwann cells formed columns which resembled bands of Bungner. They were found mainly, but not exclusively, inside the pre-existing basal lamina tubes left behind by the killed nerve fibres. Some Schwann cells secreted a thin, patchy basal lamina even though they lacked axonal contact. Schwann cell columns became partially compartmentalized by fibroblast processes. Myelin and other debris were removed most rapidly in those parts of the grafts penetrated by large numbers of Schwann cells. The maximum distance the Schwann cells penetrated into the grafts was 8.5 mm and this was achieved by 6 to 8 weeks after operation. This is about half the maximum distance migrated by Schwann cells accompanying regenerating axons through similar grafts. The reasons why Schwann cells migrate shorter distances without axons and the significance of these results for the interpretation of axonal regeneration experiments using acellular grafts are discussed.Supported by a grant from the Medical Research Council