title: FK506 enhances regeneration of axons across long peripheral nerve gaps repaired with collagen guides seeded with allogeneic Schwann cells.
abstract: We assessed the effects of FK506 administration on regeneration after a 6-mm gap repair with a collagen guide seeded with allogeneic Schwann cells (SCs) in the mouse sciatic nerve. SCs were isolated from predegenerated adult sciatic nerves and expanded in culture using a defined medium, before being seeded in the collagen guide embedded in Matrigel. Functional reinnervation was evaluated by noninvasive methods to determine recovery of motor, sensory, and autonomic functions in the hindpaw over 4 months postoperation. Histological analysis of the regenerated nerves was performed at the end of the study. Using simple collagen guides for tubulization repair, treatment with an immunosuppressant dose of FK506 (5 mg/kg/day) resulted in significant improvement of the onset and the degree of reinnervation. While the introduction of allogeneic SCs did not improve regeneration versus a collagen guide filled only with Matrigel, treatment with FK506 allowed for successful regeneration in all the mice and for significant improvement in the levels of functional recovery. Compared with the untreated group, there was greater survival of transplanted pre-labeled SCs in the FK506-treated animals. Morphologically, the best nerve regeneration (in terms of nerve caliber and numbers of myelinated axons) was obtained with SC-seeded guides from FK506-treated animals. Thus, FK506 should be considered as adjunct therapy for various types of tubulization repair.
authors.affiliation: Department of Cell Biology, Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Udina
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rodríguez
authors.forename: Enrique
authors.initials: E
authors.lastname: Verdú
authors.forename: Mónica
authors.initials: M
authors.lastname: Espejo
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Gold
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
mesh_terms: D020341:Absorbable Implants / Q000639:trends; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects* / Q000254:growth & development*; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use; D016378:Tissue Transplantation / Q000379:methods; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009414:Nerve Growth Factors; D003094:Collagen; D016559:Tacrolimus