組織工学の手法を用いた新しい分岐部人工気管の開発

2013 Fiscal Year Annual Research Report

• Project/Area Number: 25253082
• Research Category: Grant-in-Aid for Scientific Research (A)
• Research Institution: Kyoto University
• Principal Investigator: 中村 達雄 京都大学, 再生医科学研究所, 准教授 (70227908)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 気道再建 / コラーゲン / 人工気管 / 気管分岐部 / 組織工学 / コンポジット / 吻合離開 / 狭窄

Research Abstract

分岐部気管再建に用いる人工気管のフレームを形成するメッシュの素材として、従来は非吸収性のポリプロピレン製マーレックスメッシュが用いられていた。本研究では、まずその素材を生体内吸収性のポリグリコール酸、ポリ乳酸製のメッシュに変更した人工気管を作製して、ビーグル犬の頚部気管における埋入実験を行った。性能を評価したところ、吸収性のメッシュにコラーゲンを重層した材料でもそれを足場として組織を形成して、air tightな構造物になることがわかった。しかしながら、内腔保持のために入れたステントが気管壁内のメッシュが吸収するにしたがって内腔に脱落してしまうことが判明した。この分解吸収性素材による気管再建の実験は、これまでに例のない試みであったが、内腔保持材料をいかに入れるかという課題が次に残されていることが明らかになった。従来のマーレックスメッシュを用いたY字型の分岐部用の人工気管に関しては、本年度はステントの入れ方を改良したものを作製した。ビーグル犬への埋込み実験で性能を評価する。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

頚部気管用の人工気管はすでに2002年より臨床応用が始まり、甲状腺癌の気管浸潤の患者などに対して使われて、その安全性と有効性が確かめられている。本研究では胸腔内気管、とりわけ気管分岐部で安全に使用できる人工気管の開発を目指している。これまでにコラーゲンと細胞のコンポジットを用いたビーグル犬の動物実験を進めて、当初の計画より良好な所見を得ている。すなわち分岐部気管再建では、問題になる吻合部の離解や狭窄が、これまでの人工気管に比べて少ないことが判明しているからである。

Strategy for Future Research Activity

・埋込実験を継続しつつ、コラーゲンに含漬させる細胞の最適化を行う。
・分岐部人工気管の再建をN=10程度ビーグル成犬で行い、上皮化、気管壁の組織再生を評価する。
・CT撮影を行い、再建部気管内径の変化を解析し、安全性を確認する。

Research Products

• [Journal Article] The outcome of pulmonary resection for invasive fungal infection complicating haematological malignancy. (2014)
  • Author(s): Hamaji, M., Cassivi, SD., Shen, KR., Wigle, DA., Allen, MS., Nichols, FC., Deschamps, C.
  • Journal Title: Eur J Cardiothorac Surg Volume: 45 Pages: e1-5
  • DOI: 10.1093/ejcts/ezt518.
  • Peer Reviewed / Open Access
• [Journal Article] Effect of astaxanthin on vocal fold wound healing. (2014)
  • Author(s): Mizuta, M., Hirano, S., Ohno, S., Hiwatashi, N., Tateya, I., Kanemaru, S., Nakamura, T., Ito, J.
  • Journal Title: Laryngoscope. Volume: 124 Pages: E1-7
  • DOI: 10.1002/lary.24197.
  • Peer Reviewed / Open Access
• [Journal Article] A novel surgical marking system for small peripheral lung nodules based on radio frequency identification technology: Feasibility study in a canine model. (2014)
  • Author(s): Kojima, F., Sato, T., Takahata, H., Okada, M., Sugiura, T., Oshiro, O., Date, H., Nakamura, T.
  • Journal Title: J Thorac Cardiovasc Surg Volume: 147 Pages: 1384-1389
  • DOI: 10.1016/j.jtcvs.2013.05.048.
  • Peer Reviewed / Open Access
• [Journal Article] Restoration of scarred vocal folds using 5 amino acid-deleted type hepatocyte growth factor. (2014)
  • Author(s): Mizuta M, Hirano S, Ohno S, Kanemaru SI, Nakamura T, Ito J.
  • Journal Title: Laryngoscope Volume: 124 Pages: E81-6
  • DOI: 10.1002/lary.24413.
  • Peer Reviewed
• [Journal Article] Survival and treatments in patients with incompletely resected thymoma. (2014)
  • Author(s): Hamaji, M., Omasa, M., Chen, F., Yamada, T., Sato, M., Menju, T., Sato, T., Aoyama, A., Sonobe, M., Bando, T., Date, H.
  • Journal Title: Asian Thoracic and Cardiovascular Annals. Volume: in press Pages: in press
  • Peer Reviewed
• [Journal Article] Prior thoracoscopic surgery may improve reoperative pulmonary resection. (2014)
  • Author(s): Hamaji, M., Cassivi, SD., Shen, KR., Allen, MS., Nichols, FC., Deschamps, C., Wigle, DA.
  • Journal Title: Asian Thoracic and Cardiovascular Annals. Volume: in press Pages: in press
  • Peer Reviewed
• [Journal Article] Long-term follow-up of autologous bone marrow mononuclear cell transplantation following surgical decompression in a dog with chronic spinal cord injury. (2014)
  • Author(s): Tamura, K., Harada, Y., Kunimi, M., Takemitsu, H., Hara, Y., Nakamura, T., Tagawa, M.
  • Journal Title: Exp Clin Transplant Volume: in press Pages: in press
  • Peer Reviewed
• [Journal Article] Novel tracheal prosthesis using in situ Tissue Engineering. (2013)
  • Author(s): Nakamura, T., Kojima, F., Sato, T., Hamaji, M., Kaneko, M., Kanemaru, S., Nakada, A., Omori, K., Shigeno, K., Wakatsuki, M., Endo, K.
  • Journal Title: Int J Artif Organs Volume: 36 Pages: 585
  • Peer Reviewed
• [Journal Article] Regeneration of Canine Inferier Alveolar Nerve by Polyglycolic Acid-Collagen Tube with Platelet Rich Plasma. (2013)
  • Author(s): Shigeno, K., Kaneko, M., Wakatsuki, M., Nakada, A., Hashimoto, Y., Honda, M., Inada, Y., Nakamura, T.
  • Journal Title: Int J Artif Organs. Volume: 36 Pages: 571
  • Peer Reviewed
• [Journal Article] Sequential Changes of Bone Repairing in Rabbit Skull Defect Implanted Octacalcium Phosphate and Collagen Composite. (2013)
  • Author(s): Kaneko, M., Wakatsuki, M., Shigeno, K., Nakada, A., Nakamura, T.
  • Journal Title: Int J Artif Organs Volume: 36 Pages: 572
  • Peer Reviewed
• [Journal Article] Promotion of Bone Repairing by Use of Collagen Scaffold Incorporating Reconbinant Human FGF-2 in Rabbit Skull Defect Model. (2013)
  • Author(s): Wakatsuki, M., Kaneko, M.,Nakada, A., Shigeno, K., Nakamura, T.
  • Journal Title: Int J Artif Organs Volume: 36 Pages: 551
  • Peer Reviewed
• [Journal Article] Manufacture of a weakly denatured collagen fiber scaffold with excellent biocompatibility and space maintenance ability. (2013)
  • Author(s): Nakada, A., Shigeno, K., Sato, T., Kobayashi, T., Wakatsuki, M., Uji, M., Nakamura, T.
  • Journal Title: Biomed Meter. Volume: 8 Pages: 45010-45019
  • DOI: 10.1088/1748-6041/8/4/045010.
  • Peer Reviewed
• [Journal Article] Cellular interactions via conditioned media induce in vivo nephron generation from tubular epithelial cells or mesenchymal stem cells. (2013)
  • Author(s): Machiguchi, T., Nakamura, T.
  • Journal Title: Biochemical and Biophysical Research Communications. Volume: 435 Pages: 327-333
  • DOI: 10.1016/j.bbrc.2013.04.050.
  • Peer Reviewed
• [Journal Article] 生体内組織再生誘導型の人工気管を用いた気道再建. (2013)
  • Author(s): 大森孝一、多田靖宏、野本幸男、谷亜希子、金丸眞一、中村達雄
  • Journal Title: 再生医療 Volume: 12 Pages: 57-63
• [Journal Article] Evaluation of the use of induced pluripotent stem cells (iPSCs) for the regeneration of tracheal cartilage. (2013)
  • Author(s): Imaizumi, M., Nomoto, Y., Sato, Y., Sugino, T., Miyake, M., Wada, I., Nakamura, T., Omori, K.
  • Journal Title: Cell Transplantation Volume: 22 Pages: 341-353
  • DOI: 10.3727/096368912X653147.
  • Peer Reviewed
• [Journal Article] Bioengineered trachea using autologous chondrocytes for regeneration of tracheal cartilage in a rabbit model. (2013)
  • Author(s): Nomoto, M., Nomoto, Y., Tada, Y., Tani, A., Otsuki, K., Suzuki, R., Nakamura, T., Omori, K.
  • Journal Title: Laryngoscope Volume: 123 Pages: 2195-2201
  • DOI: 10.1002/lary.23784.
  • Peer Reviewed
• [Journal Article] Improvement of eustachian tube function by Tissue-Engineered regeneration of mastoid air cells. (2013)
  • Author(s): Kanemaru, S., Umeda, H., Yamashita, M., Hiraumi, H., Hirano, S., Nakamura, T., Ito, J.:
  • Journal Title: Laryngoscope. Volume: 123 Pages: 472-476
  • DOI: 10.1002/lary.23626.
  • Peer Reviewed
• [Journal Article] Functional regeneration of laryngeal muscle using bone marrow-derived stromal cells. (2013)
  • Author(s): Kanemaru, S., Kitani, Y., Ohno, S., Shigemoto, T., Kojima, T., Ishikawa, S., Mizuta, M., Hirano, S., Nakamura, T., Dezawa, M.
  • Journal Title: Laryngoscope Volume: 123 Pages: 2728-34
  • DOI: 10.1002/lary.24060.
• [Journal Article] Protracted delay in taste sensation recovery after surgical lingual nerve repair: a case report. (2013)
  • Author(s): Seo, K., Inada, Y., Terumitsu, M. Nakamura, T., Shigeno, K., Tanaka, Y., Tsurumaki, T., Kurata, S., Matsuzawa, H.
  • Journal Title: Journal of Medical Case Reports. Volume: 7 Pages: 77-81
  • DOI: 10.1186/1752-1947-7-77.
  • Peer Reviewed
• [Journal Article] Intravenous administration of adipose-derived stromal cells does not ameliorate bleomycin-induced lung injury in rats. (2013)
  • Author(s): Uji, M., Nakada, A., Nakamura, T.
  • Journal Title: Open J Regen Med. Volume: 2 Pages: 39-45
  • Peer Reviewed
• [Journal Article] Intrahepatic biliary ablation with pure ethanol: an experimental model of biliary atresia. (2013)
  • Author(s): Tatekawa, Y., Nakada, A., Nakamura, T.
  • Journal Title: Surg Today. Volume: 46 Pages: 661-669
  • DOI: 10.1007/s00595-012-0379-2.
  • Peer Reviewed
• [Journal Article] Regenerative phonosurgical treatments for vocal fold scar and sulcus with basic fibroblast growth factor. (2013)
  • Author(s): Hirano S, Mizuta M, Kaneko M, Tateya I, Kanemaru SI, Ito J.
  • Journal Title: Laryngoscope Volume: 123 Pages: 2749-55
  • DOI: 10.1002/lary.24092.
  • Peer Reviewed
• [Journal Article] An incidental and uncommon pulmonary sequestration with an uncommon feeding artery. (2013)
  • Author(s): Hamaji, M., Burt, BM., Ali, SO., Mirkovic, J.
  • Journal Title: Int J Surg Case Rep Volume: 4 Pages: 861-2
  • Peer Reviewed
• [Journal Article] A microthymoma and no germinal centre in myasthenia gravis. (2013)
  • Author(s): Hamaji, M., Vanderlaan, PA., Sugarbaker, DJ., McNamee, CJ.
  • Journal Title: Eur J Cardiothorac Surg Volume: 44 Pages: 1146-7
  • DOI: 10.1093/ejcts/ezt208.
  • Peer Reviewed
• [Journal Article] Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer. (2013)
  • Author(s): Hamaji, M., Allen, MS., Cassivi, SD., Deschamps, C., Nichols, FC., Wigle, DA., Shen, KR.
  • Journal Title: J Thorac Cardiovasc Surg Volume: 145 Pages: 683-90
  • DOI: 10.1016/j.jtcvs.2012.12.051.
  • Peer Reviewed
• [Journal Article] A personal experience of 2-year general thoracic surgery training programs in Japan and the United States. (2013)
  • Author(s): Hamaji, M., Tanaka, T.
  • Journal Title: Gen Thorac Cardiovasc Surg Volume: 61 Pages: 139-42
  • DOI: 10.1007/s11748-012-0191-3.
  • Peer Reviewed
• [Journal Article] Spontaneous diaphragm rupture associated with vaginal delivery. (2013)
  • Author(s): Hamaji, M., Burt, BM., Ali, SO., Cohen. DM.
  • Journal Title: Gen Thorac Cardiovasc Surg Volume: 61 Pages: 473-5
  • DOI: 10.1007/s11748-012-0146-8.
  • Peer Reviewed
• [Presentation] Novel tracheal prosthesis using in situ Tissue Engineering. (2013)
  • Author(s): Nakamura, T., Kojima, F., Sato, T., Hamaji, M., Kaneko, M., Kanemaru, S., Nakada, A., Omori, K., Shigeno, K., Wakatsuki, M., Endo, K.
  • Organizer: 40th Annual ESAO Congress
  • Place of Presentation: Scotland (UK)
  • Year and Date: 20130911-20130914
• [Presentation] Sequential Changes of Bone Repairing in Rabbit Skull Defect Implanted Octacalcium Phosphate and Collagen Composite. (2013)
  • Author(s): Kaneko, M., Wakatsuki, M., Shigeno, K., Nakada, A., Nakamura, T.
  • Organizer: 40th Annual ESAO Congress
  • Place of Presentation: Scotland (UK)
  • Year and Date: 20130911-20130914
• [Presentation] Regeneration of Canine Inferier Alveolar Nerve by Polyglycolic Acid-Collagen Tube with Platelet Rich Plasma. (2013)
  • Author(s): Shigeno, K., Kaneko, M., Wakatsuki, M., Nakada, A., Hashimoto, Y., Honda, M., Inada, Y., Nakamura, T.
  • Organizer: 40th Annual ESAO Congress
  • Place of Presentation: Scotland (UK)
  • Year and Date: 20130911-20130914
• [Presentation] Promotion of Bone Repairing by Use of Collagen Scaffold Incorporating Reconbinant Human FGF-2 in Rabbit Skull Defect Model. (2013)
  • Author(s): Wakatsuki, M., Kaneko, M.,Nakada, A., Shigeno, K., Nakamura, T.
  • Organizer: 40th Annual ESAO Congress
  • Place of Presentation: Scotland (UK)
  • Year and Date: 20130911-20130914
• [Presentation] Impact of Transmission Power Variation to the Position Estimation Error Performance of RFID-tag Assisted Surgery Support System． (2013)
  • Author(s): Takahata, H., Sugiura, T., Kojima, F., Sato, T., Okada, M., Oshiro, O.
  • Organizer: The 35th Annual International Conference of the Engineering in Medicine and Biology Society
  • Place of Presentation: Osaka
  • Year and Date: 20130703-20130707
• [Presentation] Sensing Elasticity from the Phase Difference of the Stepper Motor. (2013)
  • Author(s): Kawai, T., Nishio, K., Morita, Y., Nishizawa, Y., Nakamura, T.
  • Organizer: The 35th Annual International Conference of the Engineering in Medicine and Biology Society
  • Place of Presentation: Osaka
  • Year and Date: 20130703-20130707
• [Presentation] The effect of astaxanthin on vocal fold wound healing. (2013)
  • Author(s): Mizuta, M., Hirano, S., Tateya, I., Hiwatashi, N., Kanemaru, S. Ito, J.
  • Organizer: The 134th American Laryngological Association
  • Place of Presentation: Orlando (USA)
  • Year and Date: 20130410-20130411
• [Presentation] In-Vivo Localization of Micro Radio Frequency Identification Tag: Concept Proof of Novel Surgical Marking System for Small Peripheral Lung Nodule.
  • Author(s): Kojima, F., Sato, T., Takahata, H., Okada, M., Sugiura, T., Oshiro, O., Date, H., Nakamura. T.
  • Organizer: 第２１回アジア胸部心臓血管外科学会
  • Place of Presentation: 神戸
• [Presentation] Local operated detachable endo-effect of manipulator for endoscopic surgery.
  • Author(s): Nishizawa, Y., Kawai, T., Nakamura, T., Suzuki, Y.
  • Organizer: 2013Society of American Gastrointestinal and Endoscopic Surgeons
  • Place of Presentation: Baltimore (USA)
• [Presentation] Mobile-type Locally Operated Detachable End-effector Manipulator for Laparoscopic Surgery.
  • Author(s): Kawai, T., Shin, M., Horise, Y., Nisihkawa, A., Nishizawa, Y., Nakamura, T.
  • Organizer: International Journal of Computer Assisted Radiology and Surgery
  • Place of Presentation: Heidelberg (Germany)
• [Presentation] Experimental study of new vascularized composite allotransplantation: Anorectal transplantation with rats, dogs, and human cadavers.
  • Author(s): Araki, J., Nishizawa, Y., Sato, T., Naito, M., Akita, K., Tashiro, K., Iida, T., Koshima, I.
  • Organizer: 11th Meeting of the International Hand and Composite Tissue Allotransplantation Society
  • Place of Presentation: Wroctaw (Republic of Poland)
• [Presentation] Anorectal transplantation research for the stoma patients.
  • Author(s): Araki. J., Nishizawa, Y., Sato, T., Naito, M., Akita, K., Tashiro, K., Iida, T., Koshima, I.
  • Organizer: 6th European Plastic Surgery Research Council
  • Place of Presentation: Hamburg (Germany)
• [Presentation] Anorectal transplantation research with rats, dogs, and human cadavers.
  • Author(s): Araki, J., Nishizawa, Y., Sato, T., Naito, M., Akita, K., Tashiro, K., Iida, T., Koshima, I.
  • Organizer: World Society of Reconstructive Microsurgery 2013 Congress
  • Place of Presentation: Chicago (USA)
• [Remarks] 京都大学再生医科学研究所 臓器再建応用分野ホームページ
  • URL: http://www.frontier.kyoto-u.ac.jp/ca04/