FK506 enhances regeneration of axons across long peripheral nerve gaps repaired with collagen guides seeded with allogeneic Schwann cells

• Published in: Glia Vol. 47; no. 2; pp. 120 - 129
• Main Authors: Udina, Esther, Rodríguez, Francisco J., Verdú, Enrique, Espejo, Mónica, Gold, Bruce G., Navarro, Xavier
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2004; Wiley-Liss
• Subjects: Absorbable Implants - trends; Animals; Axons - drug effects; Axons - physiology; Biological and medical sciences; Cells, Cultured; cellular prosthesis; Collagen - pharmacology; Collagen - therapeutic use; Female; FK506; Fundamental and applied biological sciences. Psychology; Graft Survival - drug effects; Graft Survival - immunology; Hindlimb - innervation; Hindlimb - physiology; Immune Tolerance - drug effects; Immune Tolerance - immunology; Immunosuppressive Agents - pharmacology; Isolated neuron and nerve. Neuroglia; Mice; Nerve Growth Factors - pharmacology; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Nociceptors - physiology; Peripheral Nerve Injuries; Peripheral Nerves - drug effects; Peripheral Nerves - growth & development; Recovery of Function - drug effects; Recovery of Function - immunology; reinnervation; Schwann cell; Schwann Cells - cytology; Schwann Cells - physiology; Schwann Cells - transplantation; Sciatic Nerve - cytology; Sciatic Nerve - physiology; Sciatic Nerve - transplantation; Sciatic Neuropathy - drug therapy; Sciatic Neuropathy - immunology; Sciatic Neuropathy - physiopathology; Tacrolimus - pharmacology; Tacrolimus - therapeutic use; Tissue Transplantation - methods; Treatment Outcome; tube repair; Vertebrates: nervous system and sense organs; Peripheral nerve; Glial cell; Neuroglia; Glycoprotein; Central nervous system; tube repair; Axon; FK506; Regeneration; cellular prosthesis; Tacrolimus; Schwann cell; Collagen; reinnervation; Repair
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.20025

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. © 2004 Wiley‐Liss, Inc.