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FK506 enhances regeneration of axons across long peripheral nerve gaps repaired with collagen guides seeded with allogeneic Schwann cells
Author(s) -
Udina Esther,
Rodríguez Francisco J.,
Verdú Enrique,
Espejo Mónica,
Gold Bruce G.,
Navarro Xavier
Publication year - 2004
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20025
Subject(s) - reinnervation , regeneration (biology) , sciatic nerve , matrigel , axon , schwann cell , biology , nerve guidance conduit , anatomy , pathology , medicine , microbiology and biotechnology , in vitro , biochemistry
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.