日本臨床麻酔学会 vol.33

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1 507 日本臨床麻酔学会第 32 回大会招待講演日臨麻会誌 Vol.33 No.4, , 2013 人工神経管 (PGA-C tube) による末梢神経再生と in situ Tissue Engineering( 生体内再生 ) 慢性神経因性疼痛は脳の錯覚か? * 中村達雄 [ 要旨 ] 人工神経管 (PGA-C tube) を用いた再生医学の臨床応用が 2002 年より始まっている. この再生医療を支えるのが in situ Tissue Engineering( 生体内再生 ) の概念である.in situ Tissue Engineering は欠損した組織を生体内のその部位 (in situ) で再生させる手法で世界に先駆けて本邦で提唱された. 末梢神経は再生能力を有するが, 人工神経 PGA-C tubeは神経再生の場を PGA チューブの内腔に有する医療器具である. これまでに再建した末梢神経は合計 300 本を超え, また神経因性疼痛に対しても効果があることが判明し, 新たな治療法として期待が高まっている. キーワード : 人工神経, 神経誘導管, 末梢神経再生, 神経因性疼痛, 生体内再生 (in situ Tissue Engineering) Ⅰ 末梢神経の再生能 : 再生能と防御戦略 Santiago Ramón Y Cajal 19 NOGO NI

2 508 Vol.33 No.4/Jul Ⅱ 末梢神経の外科的再建 5mm 5mm 5mm neuromuscular junction 1 Ⅲ チューブによる神経再建 Göran Lundborg Lundborg 3 Ⅳ 吸収性神経連結管 ( 人工神経 ) の開発 PGA PLA NEUROTUBE 図 1 PGA FDA Neurotube 30mm

FDA 7 Ⅴ 再生の場の理論と人工神経の内部構造 IV IV nerve growth factor NGF 5 6 7

3 509 図 1 米国で販売されている PGA 製人工神経 (Neurotube) 図 2 PGA-C tube 内コラーゲンの薄フィルム多房状構造 (SEM 所見 ) 4 extracellular matrix ECM NeuraGen FDA 7 Ⅴ 再生の場の理論と人工神経の内部構造 IV IV nerve growth factor NGF PGA-C tube 図 2 Ⅵ in situ Tissue Engineering と新しく開発された人工神経 (PGA-C tube) PGA-C tube

4 510 Vol.33 No.4/Jul Ⅶ 人工神経と再生の場の理論図 3 PGA-C tube 3mm Tissue Engineering 3 in situ Tissue Engineering PGA-C tube 20 80mm 8 15mm PGA-C tube 9 PGA-C tube 図 in situ Tissue Engineering 1 2 Ⅷ 人工神経の埋入手術手技 Ⅸ 人工神経 (PGA-C tube) による末梢神経再生医療

5 511 patient selection Ⅹ 神経因性疼痛に対する新たな治療法 complex regional pain syndrome CRPS 11, Silas Weir Mitchell 参考文献 1) Bandtlow CE, Schwab ME:NI-35/250/Nogo-A:a neurite growth inhibitor restricting structural plasticity and regeneration of nerve fibers in the adult vertebrate CNS. Glia 29: , ) Foramitti C:Zur technik der nervenaht. Arch Klin Chir 73: , ) Dahlin LB, Lundborg G:Nerve repair:experimental and clinical update, Tendon, Nerve and Other Disorders(Surgery of Disorders of the Hand and Upper Extremity). Edited by Tubiana R, Gilbert A. Taylor & Francis, London, 2004, ) Weber RA, Breidenbach WC, Brown RE, et al.:a randomized prospective study of polyglycolic acid conduits for digital nerve reconstruction in humans. Plast Reconstr Surg 106: , ) Mohammad JA, Warnke PH, Pan YC, et al.:increased axonal regeneration through a biodegradable amnionic tube nerve conduit:effect of local delivery and incorporation of nerve growth factor/hyaluronic acid media. Ann Plast Surg 44:59-64, ) Rodríguez FJ, Verdú E, Ceballos D, et al.:nerve guides seeded with autologous schwann cells improve nerve regeneration. Exp Neurol 161: , ) Toba T, Nakamura T, Shimizu Y, et al.:regeneration of canine peroneal nerve with the use of a polyglycolic acid-collagen tube filled with laminin-soaked collagen sponge:a comparative study of collagen sponge and collagen fibers as filling materials for nerve conduits. J Biomed Mater Res 58: , 2001

6 512 Vol.33 No.4/Jul ) Matsumoto K, Ohnishi K, Kiyotani T, et al.: Peripheral nerve regeneration across an 80-mm gap bridged by a polyglycolic acid(pga)-collagen tube filled with laminin-coated collagen fibers:a histological and electrophysiological evaluation of regenerated nerves. Brain Res 868: , ) Nakamura T, Inada Y, Fukuda S, et al.:experimental study on the regeneration of peripheral nerve gaps through a polyglycolic acid-collagen(pga-collagen) tube. Brain Res 1027:18-29, ) 萩原明於, 山岸久一, 清水慶彦 : 再発直腸癌手術の神経合併切除における新しい神経機能再建. 治療 84: , )Inada Y, Morimoto S, Takakura Y, et al.:regeneration of peripheral nerve gaps with a polyglycolic acidcollagen tube. Neurosurgery 55: , )Inada Y, Morimoto S, Moroi K, et al.:surgical relief of causalgia with an artificial nerve guide tube:successful surgical treatment of causalgia(complex Regional Pain Syndrome Type II)by in situ tissue engineering with a polyglycolic acid-collagen tube. Pain 117: , )Seo K, Inada Y, Terumitsu M, et al.:one year outcome of damaged lingual nerve repair using a PGAcollagen tube:a case report. J Oral Maxillofac Surg 66: , )Kanemaru S, Nakamura T, Omori K, et al.:recurrent laryngeal nerve regeneration by tissue engineering. Ann Otol Rhinol Laryngol 112: , 2003 Regeneration of Peripheral Nerve on PGA-C Tube and in situ Tissue Engineering Tatsuo NAKAMURA Institute for Frontier Medical Sciences, Kyoto University Clinical application of the PGA-C tube began in Japan in This article involves a brief summary of the clinical results and the concept of in situ tissue engineering and field theory, which is the background of this novel therapy. A clinical trial of the PGA-C tube for neuropathic pain is also discussed in this article. In situ tissue engineering was first proposed in Japan in 2000 as a new concept in which, a defected tissue is fabricated not in the incubator but in the body. A peripheral nerve has strong potential to regenerate, so if an adequate field for regeneration is provided in our body, it recovers easily. The PGA-C tube is a bio-absorbable tube stuffed with collagen. The collagen with a structure of multilayed thin films provides an adequate scaffold for tissue regeneration. To date, over 300 PGA-C tubes have been used, and surprisingly good results have been obtained after the peripheral nerve repair. Interestingly, the PGA-C tube is effective for patients who suffered from neuropathic pain. Thus this new device, the PGA-C tube, might be promising for further clinical application. Key Words : Artificial nerve, Nerve conduit, Regeneration, Neuropathic pain, in situ tissue engineering The Journal of Japan Society for Clinical Anesthesia Vol.33 No.4, 2013

人工神経

Tatsuo NAKAMURA 1. はじめに BAHA 2013 1 1 brain computer interface 1) motor function 著者連絡先 606-850753 E-mail. nakamura@frontier.kyoto-u.ac.jp 2) 4) 2. 人工神経開発のベースとなるin situ Tissue Engineeringという概念 Tissue Engineering