title: Exogenous leukaemia inhibitory factor enhances nerve regeneration after late secondary repair using a bioartificial nerve conduit.
abstract: The clinical outcome of peripheral nerve injuries remains disappointing, even in the ideal situation of a primary repair performed with optimal microsurgical techniques. Primary repair is appropriate for only about 85% of injuries, and outcome is worse following secondary nerve repair, partly owing to the reduced regenerative potential of chronically axotomised neurons. Leukaemia inhibitory factor (LIF) is a gp-130 neurocytokine that is thought to act as an 'injury factor', triggering the early-injury phenotype within neurons and potentially boosting their regenerative potential after secondary nerve repair. At 2-4 months after sciatic nerve axotomy in the rat, 1 cm gaps were repaired using either nerve isografts or poly-3-hydroxybutyrate conduits containing a calcium alginate and fibronectin hydrogel. Regeneration was determined by quantitative immunohistochemistry 6 weeks after repair, and the effect of incorporating recombinant LIF (100 ng/ml) into the conduits was assessed. LIF increased the regeneration distance in repairs performed after both 2 months (69%, P=0.019) and 4 months (123%, P=0.021), and was statistically comparable to nerve graft. The total area of axonal immunostaining increased by 21% (P>0.05) and 63% (P>0.05), respectively. Percentage immunostaining area was not increased in the 2 months group, but increased by 93% in the repairs performed 4 months after axotomy. Exogenous LIF, therefore, has a potential role in promoting peripheral nerve regeneration after secondary repair, and can be effectively delivered within poly-3-hydroxybutyrate bioartificial conduits used for nerve repair.
authors.affiliation: Blond-McIndoe Centre, Royal Free and University College Medical School, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: McKay Hart
authors.forename: M
authors.initials: M
authors.lastname: Wiberg
authors.forename: G
authors.initials: G
authors.lastname: Terenghi
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D006085:Graft Survival; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006885:Hydroxybutyrates / Q000627:therapeutic use; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D011091:Polyesters / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries* / Q000502:physiology / Q000601:surgery; D013997:Time Factors; D000094122:Polyhydroxybutyrates
chemical_list: D006131:Growth Inhibitors; D006885:Hydroxybutyrates; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D011091:Polyesters; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates