Effects of Schwann cell transplants in an experimental nerve amputee model.
OBJECTIVE
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.


CONCLUSIONS
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.
Lago
Natalia
N
Department of Cell Biology, Physiology and Immunology, and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Casas
Caty
C
Muir
Elizabeth M
EM
Rogers
John
J
Navarro
Xavier
X
D000704:Analysis of Variance; D000818:Animals; D019771:Axotomy / Q000379:methods; D002461:Cell Line, Transformed / Q000637:transplantation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D048091:Guided Tissue Regeneration; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009416:Nerve Regeneration; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology* / Q000637:transplantation*; D020426:Sciatic Neuropathy / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009418:S100 Proteins