Schwann-Cell Proliferation in Muscle-Vein Combined Conduits for Bridging Rat Sciatic Nerve Defects

ABSTRACT

Among the various grafting procedures that have been studied as alternatives to traditional fresh nerve autografts for the repair of severed peripheral nerves, muscle-vein-combined graft conduits have recently been devised and successfully employed. In the present study, the early presence, origin, and proliferation activity of Schwann cells (SCs) along this particular type of biological graft conduit have been investigated, using antibodies directed against glial fibrillar acid protein (GFAP), a protein that is specifically expressed in glial cells, and proliferating cell nuclear antigen (PCNA), a protein that is expressed by cells during DNA synthesis. Results showed that the muscle-vein-combined graft was progressively invaded by a number of GFAP-immunopositive SCs, many of which were also found to be immunopositive for PCNA, thus demonstrating that their proliferation continues to occur inside the graft. Among the molecules that could be involved in the stimulation of Schwann-cell proliferation is neuregulin-1 (NRG-1) that mediates its effects by binding to the ErbB receptor tyrosine kinase family. In the present study, the authors report on the RT-PCR analysis for NRG-1 and ErbB3 mRNAs, showing an overall increase in the content of these transcripts inside the muscle-vein-combined graft. These results suggest that the muscle-vein-combined graft conduit constitutes an environment favorable to potentiate Schwann-cell proliferation during the early regeneration phases.

KEYWORDS

Nerve repair - muscle-vein-combined conduits - Schwann cells

REFERENCES

• 1 Strauch B. Use of nerve conduits in peripheral nerve repair.  Hand Clin . 2000;  16 123-130
• 2 Dahlin L B, Lundborg G. Use of tubes in peripheral nerve repair.  Neurosurg Clin N Am . 2001;  12 341-352
• 3 Meek M F, Coert J H. Clinical use of nerve conduits in peripheral-nerve repair: review of the literature.  J Reconstr Microsurg . 2002;  18 97-109
• 4 Williams L R, Longo F M, Powell H C, Lundborg G, Varon S. Spatial-temporal progress of peripheral nerve regeneration within a silicone chamber: parameters for a bioassay.  J Comp Neurol . 1983;  218 460-470
• 5 Feneley M R, Fawcett J W, Keynes R J. The role of Schwann cells in the regeneration of peripheral nerve axons through muscle basal lamina grafts.  Exp Neurol . 1991;  114 275-285
• 6 Enver M K, Hall S M. Are Schwann cells essential for axonal regeneration into muscle autografts?.  Neuropathol Appl Neurobiol . 1994;  20 587-298
• 7 Frostick S P, Yin Q, Kemp G J. Schwann cells, neurotrophic factors, and peripheral nerve regeneration.  Microsurgery . 1998;  18 397-405
• 8 Strauch B, Rodriguez D M, Diaz J. et al . Autologous Schwann cells drive regeneration through a 6-cm autogenous venous nerve conduit.  J Reconstr Microsurg . 2001;  17 589-599
• 9 Mosahebi A, Fuller P, Wiberg M, Terenghi G. Effect of allogeneic Schwann cell transplantation on peripheral nerve regeneration.  Exp Neurol . 2002;  173 213-223
• 10 Dubovy P, Svizenska I. Migration of Schwann cells from the distal stump of the sciatic nerve 1 week after transection: the effects of insulin and cytosine arabinoside.  Glia . 1992;  6 281-288
• 11 Bryan D J, Wang K K, Summerhayes C. Migration of Schwann cells in peripheral-nerve regeneration.  J Reconstr Microsurg . 1999;  15 591-596
• 12 Fornaro M, Tos P, Geuna S, Giacobini-Robecchi M G, Battiston B. Confocal imaging of Schwann cell migration along muscle-vein-combined grafts used to bridge nerve defects in the rat.  Microsurgery . 2001;  21 153-155
• 13 Brunelli G, Battiston B, Vigasio A, Brunelli G, Marocolo D. Bridging nerve defects with combined skeletal muscle and vein conduits.  Microsurgery . 1993;  14 247-251
• 14 Battiston B, Tos P, Cushway T M, Geuna S. Nerve repair by means of vein filled with muscle grafts. I. Clinical results.  Microsurgery . 2000;  20 32-36
• 15 Battiston B, Tos P, Geuna S, Giacobini-Robecchi M G, Guglielmone R. Nerve repair by means of vein filled with muscle grafts. II. Morphological analysis of regeneration.  Microsurgery . 2000;  20 37-41
• 16 Geuna S, Tos P, Battiston B, Guglielmone R, Giacobini-Robecchi M G. Morphological analysis of peripheral nerve regenerated by means of vein grafts filled with fresh skeletal muscle.  Anat Embryol . 2000;  201 475-482
• 17 Geuna S, Tos P, Battiston B, Guglielmone R, Giacobini-Robecchi M G. A stereological study of long-term regeneration of rat severed sciatic nerve repaired by means of muscle-vein-combined grafts.  Ital J Anat Embryol . 2000;  105 65-73
• 18 Tos P, Battiston B, Geuna S. et al . Tissue specificity in rat peripheral nerve regeneration through combined skeletal muscle and vein conduit grafts.  Microsurgery . 2000;  20 65-71
• 19 Garratt A N, Britsch S, Birchmeier C. Neuregulin, a factor with many functions in the life of a Schwann cell.  BioEssays . 2000;  22 987-996
• 20 Wen D, Suggs S, Karunagaran D. et al . Structural and functional aspects of the multiplicity of Neu differentiation factors.  Mol Cell Biol . 1994;  1909 1919
• 21 Wolf H K, Dittrich K L. Detection of proliferating cell nuclear antigen in diagnostic histopathology.  J Histochem Cytochem . 1992;  40 1269-1273
• 22 Adlkofer K, Lai C. Role of neuregulins in glial cell development.  Glia . 2000;  29 104-111