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Nerve Replacement Strategies for Cavernous Nerves
F. May, M. Vroemen, K. Matiasek, J. Henke, T. Brill, A. Lehmer, M. Apprich, W. Erhardt, S. Schoeler, R. Paul, A. Blesch, R. Hartung, B. Gansbacher, N. Weidner European Urology Volume 48, Issue 3, Pages (September 2005) DOI: /j.eururo Copyright © 2005 Elsevier B.V. Terms and Conditions
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Fig. 1 Schwann cells form a mechanical scaffold for axons to grow along and secrete neurotrophic factors expressed on the cell surfaces. The trophic factors are picked up in the growth cones, incorporated in the axon, and are transported retrogradely to the nerve cell body to support neuronal survival and improve the axonal regeneration. European Urology , DOI: ( /j.eururo ) Copyright © 2005 Elsevier B.V. Terms and Conditions
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Fig. 2 (A) Nerve autografts do not offer an optimal environment for the advancing axonal sprouts: A nerve graft consists of a dense structure which may hamper the outgrowth of axons. Moreover, two suture lines double the risk of nerve fibers growing out at that suture line and cross the junction between the proximal and distal nerve stump. Therefore, injured axons may not necessarily regrow through the nerve transplant, but rather around it, failing to find and reinnervate the target area. Intraneural scarring further inhibits directional growth. (B) Nerve guidance channels do not allow the irregular sprouting of regenerating axons, but rather guide them directly to the original target area and prevent intraneural scarring. Nerve guides can be tissue-engineered on the basis of a suitable scaffold acting in concert with cells and neurotrophic factors. Neurotrophic factors, stimulating axonal growth, can be incorporated in the scaffold and can also be supplied by cells seeded into the stroma. European Urology , DOI: ( /j.eururo ) Copyright © 2005 Elsevier B.V. Terms and Conditions
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Fig. 3 (A–C) The generation of autologous Schwann cell cultures requires a peripheral nerve biopsy followed by cell culture. Magnetic-activated cell separation (MACS) of p75 low affinity nerve growth factor receptor (p75LNGFr) expressing cells allows the reliable purification of Schwann cells within 9 days after biopsy employing direct selection of Schwann cells rather than fibroblast depletion assays (Ref. [36]). In contrast to fibroblasts, Schwann cells express a receptor for Nerve Growth Factor (NGF) on their cell surface. Incubation of a magnetically conjugated antibody against this receptor allows the rapid purification process. European Urology , DOI: ( /j.eururo ) Copyright © 2005 Elsevier B.V. Terms and Conditions
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Fig. 4 (A–F) Comparison of GDNF-hypersecreting Schwann cell graft (A) versus GFP-transduced Schwann cell graft (C) and unseeded conduit (E) 12 weeks after interposition grafting (assembled photographs from electron micrographs forming a mosaic picture at magnifications of 3400×). At higher magnification (from the boxed area in A) multiple unmyelinated and myelinated sprouts can be detected (B). The histological results clearly demonstrate advanced nerve regeneration within GDNF-transduced Schwann cell seeded nerve guides with larger regenerating nerve fascicles containing abundant unmyelinated and myelinated regenerating axons, sparse extracellular matrix and a tight oligolamellar perineurium. Compared to unseeded nerve guides (E) which show only sparse minifascicles and much undifferentiated matrix (F), GFP-transduced Schwann cell grafts (C) contain large neural areas consisting of multiple regenerating axons (D). European Urology , DOI: ( /j.eururo ) Copyright © 2005 Elsevier B.V. Terms and Conditions
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