Adenoviral vector-mediated expression of a foreign gene in peripheral nerve tissue bridges implanted in the injured peripheral and central nervous system

Axons of the CNS do normally not regenerate after injury, in contrast to ax ons of the PNS. This is due to a different microenvironment at the site of the lesion as well as a particular intrinsic program of axonal regrowth. Al though transplantation of peripheral nerve tissue bridges is perhaps the mo st successful approach to promoting regeneration in the CNS, ingrowth of CN S nerve fibers with such transplants is Limited. Genetic modification of pe ripheral nerve bridges to overexpress outgrowth-promoting proteins should, in principle, improve the permissive properties of peripheral nerve transpl ants. The present study shows that pieces of peripheral intercostal nerve, subjected to ex vivo adenoviral vector-mediated gene transfer and implanted as nerve bridges in transected sciatic nerve, avulsed ventral root, hemi-s ected spinal cord and intact brain, are capable of expressing a foreign gen e. In, vitro studies showed expression of the reporter gene LacZ up to 30 d ays in Schwann cells. After implantation, LacZ expression could be detected at 7 days postimplantation, but had virtually disappeared at 14 days. Schw ann cells of the transduced nerve bridges retained the capacity of guiding regenerative peripheral and central nerve fiber ingrowth. Transduction of i ntercostal nerve pieces prior to implantation should, in principle, enable enhanced local production of neurotrophic factors within the transplant and has the potential to improve the regeneration of injured axons into the gr aft. (C) 1999 Academic Press.