CELLULAR MIGRATION AND AXONAL OUTGROWTH FROM ADULT MAMMALIAN PERIPHERAL-NERVES IN-VITRO

It is known that following peripheral nerve transections, sheath cells proliferate and migrate to form a bridge between nerve stumps, which may facilitate axonal regeneration. In the present investigations, cel lular migration and axonal outgrowth from nerves of adult mice were st udied in vitro using collagen gels. During the first 3 days in culture , profuse migration of fibroblasts and macrophages occurred from the e nds of sciatic nerve segments, which had been lesioned in situ a few d ays prior to explantation, but not from segments of normal nerves. The mechanism of cellular activation in the lesioned nerves was not deter mined, but migration was blocked by suramin, which inhibits the action s of several growth factors. The migrating cells, which form the bridg e tissue, may promote axonal regeneration in two ways. Firstly, axonal outgrowth from isolated intercostal nerves was significantly increase d in co-cultures with bridges from lesioned sciatic nerves. This stimu latory effect was inhibited by antibodies to 2.5S nerve growth factor. Secondly, the segments of bridge tissue contracted when removed from animals. It is possible that fibroblasts within the bridge exert tract ion that would tend to pull the lesioned stumps of peripheral nerve to gether, as in the healing of skin wounds. The traction may also influe nce deposition of extracellular matrix materials, such as collagen fib rils, which could orient the growth of the regenerating axons toward t he distal nerve stump. (C) 1996 John Wiley & Sons, Inc.