Gene transfer to Schwann cells after peripheral nerve injury: a delivery system for therapeutic agents.
We transferred a reporter gene to Schwann cells to test whether they might serve as an endoneurial delivery system for therapeutic proteins. A replication-defective adenoviral vector carrying the gene for beta-galactosidase (lacZ) was injected into the distal segment of intact or crushed sciatic nerves of adult rats, and the expression of lacZ was histochemically assessed. Less than 1% of the Schwann cells became reactive in intact nerves, but up to 18% of the proliferating Schwann cells of injured nerves expressed lacZ. Gene expression decayed with time but might persist for up to 2 months. It was enhanced by immunosuppression: daily cyclosporin A injections reduced both proliferation of Schwann cells and lymphocytic infiltration of the nerve, whereas tolerance induced by a single intrathymic injection of the vector 4 days after birth abolished the inflammatory response but not the proliferation of Schwann cells. The vector itself did not impede axonal regeneration. The results indicate that adenoviral gene transfer to Schwann cells in injured nerves is possible and suggest that induced production of neurotrophic factor may represent a therapeutic supplement to surgical nerve repair.
Sørensen
J
J
Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.
Haase
G
G
Krarup
C
C
Gilgenkrantz
H
H
Kahn
A
A
Schmalbruch
H
H
D000818:Animals; D016503:Drug Delivery Systems; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D008214:Lymphocytes / Q000473:pathology; D059348:Peripheral Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000473:pathology / Q000637:transplantation*; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology / Q000601:surgery; D014855:Wallerian Degeneration; D014949:Wounds, Nonpenetrating / Q000473:pathology*