Enhancement of axon growth by detergent-extracted nerve grafts.

BACKGROUND The immunogenicity of nerve allografts is responsible for their rejection. We have developed a method for preparing cell-free nerve grafts using lysophosphatidylcholine to remove cells, axons, and myelin sheaths. METHODS The remaining intact nerve extracellular matrix is the extracted nerve graft (eNG). Cultured neonatal Schwann cells were micro-injected into the eNG to form recellularized nerve grafts (rNG). eNG, rNG, and normal isografts (15 mm long) were implanted in the peroneal nerves of F-344 rats. Ten rats were given an eNG on the right, and an isograft on the left. Ten rats were given an rNG on the right, and a sham operation on the left. Sham operation was used as the control and the isograft was used as the benchmark procedure. Walking track analysis was performed every 15 days after surgery to determine the peroneal functional index. Morphometric analysis of the distal peroneal nerve and extensor digitorum muscle weight were analyzed 3 months after surgery. RESULTS The three types of grafted legs had the classical effect observed after peripheral nerve repair, with decreased functional ability, decreased target muscle weight, fewer large nerve fibers, and more small nerve fibers. Isografts, eNG, and rNG all had similar patterns of peroneal functional index improvement after implantation. The extensor digitorum longus muscle weight and axon counts for the three types of graft were not statistically different. Hence, eNG and rNG can enhance nerve regeneration in the same way as isografts. The host Schwann cells that invaded the implanted eNG probably acted in the same fashion as the cultured Schwann cells injected into the rNG and the resident cells of isografts. CONCLUSIONS The great permeability of the longitudinally oriented matrix of eNG to cells is, therefore, a major advantage over the reported poor permeability of freeze-thawed nerve grafts.

[1]  V. Hentz,et al.  A composite nerve graft system: Extracted rat peripheral nerve injected with cultured Schwann cells , 1996, Muscle & nerve.

[2]  A. K. Gulati IMMUNOLOGICAL FATE OF SCHWANN CELL‐POPULATED ACELLULAR BASAL LAMINA NERVE ALLOGRAFTS , 1995, Transplantation.

[3]  S. Mackinnon,et al.  Monoclonal antibodies against ICAM‐1 and LFA‐1 prolong nerve allograft survival , 1995, Muscle & nerve.

[4]  S. Mackinnon,et al.  The peripheral nerve allograft: A comprehensive review of regeneration and neuroimmunology , 1994, Progress in Neurobiology.

[5]  K. Tohyama,et al.  Regeneration through nerve allografts in the cynomolgus monkey (Macaca fascicularis). , 1991, The Journal of bone and joint surgery. American volume.

[6]  R. Mirsky,et al.  The effects of cAMP on differentiation of cultured Schwann cells: progression from an early phenotype (04+) to a myelin phenotype (P0+, GFAP-, N-CAM-, NGF-receptor-) depends on growth inhibition , 1991, The Journal of cell biology.

[7]  M. Turmaine,et al.  The role of Schwann cells and basal lamina tubes in the regeneration of axons through long lengths of freeze‐killed nerve grafts , 1990, Neuropathology and applied neurobiology.

[8]  G Stoll,et al.  Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation , 1989, Journal of neurocytology.

[9]  A L Dellon,et al.  Selection of the Appropriate Parameter to Measure Neural Regeneration , 1989, Annals of plastic surgery.

[10]  S. Mackinnon,et al.  Functional Evaluation of Complete Sciatic, Peroneal, and Posterior Tibial Nerve Lesions in the Rat , 1989, Plastic and reconstructive surgery.

[11]  S. Hall THE EFFECT OF INHIBITING SCHWANN CELL MITOSIS ON THE RE‐INNERVATION OF ACELLULAR AUTOGRAFTS IN THE PERIPHERAL NERVOUS SYSTEM OF THE MOUSE , 1986, Neuropathology and applied neurobiology.

[12]  S. Hall REGENERATION IN CELLULAR AND ACELLULAR AUTOGRAFTS IN THE PERIPHERAL NERVOUS SYSTEM , 1986, Neuropathology and applied neurobiology.

[13]  M. Raff,et al.  Studies on cultured rat Schwann cells. I. Establishment of purified populations from cultures of peripheral nerve , 1979, Brain Research.

[14]  A. K. Gulati,et al.  Evaluation of acellular and cellular nerve grafts in repair of rat peripheral nerve. , 1988, Journal of neurosurgery.