Affiliations: Department of Cell Biology, Physiology and Immunology,
and Institute of Neurosciences, Universitat Autònoma de Barcelona,
Bellaterra, Spain | Centro de Investigación Biomédica en Red sobre
Enfermedades Neurodegenerativas (CIBERNED), Spain | Department of Physiology, Development &
Neuroscience, University of Cambridge, Cambridge, UK
Note: [] Corresponding author: Xavier Navarro, Group of Neuroplasticity
and Regeneration, Faculty of Medicine, Universitat Autònoma de Barcelona,
E-08193 Bellaterra, Spain. Tel.: +34 935811966; E-mail: xavier.navarro@uab.cat
Abstract: Purpose: By using a nerve amputee model of the rat sciatic nerve
(Lago and Navarro, 2007), we have tested a strategy for the long-term
maintenance of regenerated axons without distal target reinnervation, by
grafting Schwann cells (SCs) into a capped silicone chamber containing the
ending nerve stump. Methods: The sciatic nerve of rats was transected and repaired
with a silicone tube, the distal nerve was again cut at 10 mm and inserted in a
capped tube that was filled with saline or with a suspension of cultured SCs.
Transplants of SCs obtained from primary cultures have been compared with those
of an immortalized SC line (SCTM41) or the same line overexpressing GDNF. Results: The histological results show that nerve fibers were
able to regenerate through a short distal nerve segment ending into the capped
chamber, and sustain distal branches without degenerating for several months.
There was abundant axonal sprouting forming an ending neuroma, and the caliber
of myelinated fibers remained far thinner than normal during the 9 months
investigated. With a distal transplant of primary SCs there were significantly
more regenerated myelinated fibers than in the control group at 9 months,
indicating that the grafted cells stimulated the axonal growth response and
helped to maintain survival of axon branches. In contrast, axonal regeneration
was significantly reduced with grafts of SCTM41 cells, probably due to physical
competition between cell proliferation and axonal growth. SCTM41 cells
overexpressing GDNF improved the regenerative response with respect to the
parent SCTM41 cells, although not to the same extent as the primary SCs. Conclusion: A graft of primary SCs in the capped chamber
stimulated axonal growth response and/or maintained survival of axonal branches
on the long term in the nerve amputee model.
