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Development of xenogeneic decellularized biotubes for off-the-shelf applications

Research Project

Project/Area Number 16K10438
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Yamanami Masashi  京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (30438204)

Co-Investigator(Kenkyū-buntansha) 坂井 修  京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (10298432)
渡辺 太治  京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (20448723)
神田 圭一  京都府立医科大学, 医学(系)研究科(研究院), 講師 (60295649)
夜久 均  京都府立医科大学, 医学(系)研究科(研究院), 教授 (50295648)
上 大介  京都府立医科大学, 医学(系)研究科(研究院), 講師 (80415588)
五條 理志  京都府立医科大学, 医学(系)研究科(研究院), 教授 (90316745)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords組織工学 / 脱細胞 / 結合組織 / 血管移植片 / 小口径人工血管 / 異種移植 / 結合組織管 / 脱細胞処理 / 同種移植 / 循環系移植片 / 小口径代用血管 / 生体内組織工学 / バイオチューブ / 生体内組織形成術
Outline of Final Research Achievements

We have developed in vivo tissue-engineered, autologous, small-caliber vascular grafts, called “biotubes”. However, biotubes preparation takes 4 weeks, therefore, biotubes cannot be applied in emergency situations. The aim of this study was to develop xenogeneic decellularized biotubes.
Silicone rod molds placed in subcutaneous pouches of a beagle dog for 4 weeks were harvested with their surrounding connective tissues. Tubular connective tissues were obtained after pulling out the molds. They were decellularized with detergents. The decellularized grafts were xenogeneically transplanted to the abdominal aortas of rats. Echocardiography confirmed the patency of the grafts at 1 month after implantation. Histological evaluation revealed that the grafts formed neointima on the luminal surface, and that the graft walls had cell infiltration. This technology enables the easy fabrication of grafts from xenogeneic animals in advance, satisfying the conditions for off-the-shelf grafts.

Academic Significance and Societal Importance of the Research Achievements

本技術により異種動物体内で各種サイズの代用血管を大量に作製し保存しておくことができ、緊急手術も要求される心臓血管外科領域で『必要なときにいつでも使える自己再生型小口径代用血管』としての需要が見込まれる。
抗原性を除去した結合組織管は血管再生における足場材料として有用であることが期待され、移植後早期に自家組織による血管壁再構築が見られ、生体の治癒力を最大限に引き出し、早期治癒・迅速な内皮化による強力な抗血栓性を獲得するなど小口径代用血管を高い再現性で形成する技術として、現在の循環器系人工臓器の様々な問題点を克服するためのブレイクスルーになることが期待できる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (37 results)

All 2020 2019 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (32 results) (of which Int'l Joint Research: 19 results)

  • [Journal Article] EFFECTS OF SHORT PERIOD OF CHEMICAL MODIFICATION ON PORCINE PERICARDIUM2019

    • Author(s)
      Inoue T, Kanda K, Yamanami M, Kami D, Gojo S, Yaku H.
    • Journal Title

      Int J Artif Organs

      Volume: 42 Pages: 391-391

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MODIFICATIONS OF MECHANICAL PROPERTIES OF IN VIVO TISSUE ENGINEERED VASCULAR TISSUES BY SHORT PERIOD OF CHEMICAL TREATMENTS2019

    • Author(s)
      Inoue T, Kanda K, Yamanami M, Kami D, Gojo S, Yaku H.
    • Journal Title

      Int J Artif Organs

      Volume: 42 Pages: 392-392

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] APPLICATION OF IN VIVO TISSUE ENGINEERED DECELLULARIZED CONNECTIVE TISSUE FOR CARDIOVASCULAR GRAFTS2019

    • Author(s)
      Yamanami M, Kanda K, Morimoto K, Inoue T, Watanabe T, Sakai O, Kami D, Gojo S, Yaku H.
    • Journal Title

      Int J Artif Organs

      Volume: 42 Pages: 444-444

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IN VIVO TISSUE ENGINEERED VASCULAR GRAFTS ADAPTABLE TO AV SHUNTS2019

    • Author(s)
      Kanda K, Yamanami M, Inoue T, Watanabe T, Sakai O, Kami D, Gojo S, Yaku H.
    • Journal Title

      Int J Artif Organs

      Volume: 42 Pages: 454-454

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of xenogeneic decellularized biotubes for off-the-shelf applications2019

    • Author(s)
      Yamanami Masashi,Kanda Keiichi,Kawasaki Takanori,Kami Daisuke,Watanabe Taiji,Gojo Satoshi,Yaku Hitoshi
    • Journal Title

      Artificial Organs

      Volume: 印刷中 Issue: 8 Pages: 773-779

    • DOI

      10.1111/aor.13432

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Clinical Application of an In-Vivo Tissue-Engineered Vascular Graft in a Patient with MAPCA: Evaluation of the Mechanical Properties and Histology2020

    • Author(s)
      Fujita S, Yamagishi M, Kanda K, Maeda Y, Inoue T, Yamanami M, Watanabe T, Konishi E, Takeda N, Yaku H.
    • Organizer
      the Society of Thoracic Surgeons 56th Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 4-YEAR FOLLOW-UP OF THE FIRST CLINICAL APPLICATION OF THE IN VIVO TISSUE ENGINEERED VASCULAR GRAFT TO CONGENITAL HEART DISEASE: POTENTIAL FOR ADAPTABILITY TO PATIENT2019

    • Author(s)
      Fujita S, Yamagishi M, Kanda K, Maeda Y, Yamanami M, Watanabe T, Yaku H.
    • Organizer
      the Combined International Symposium for Applied Cardiovascular Biology and Vascular Tissue Engineering (ISACB+ISVTE 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EFFECTS OF SHORT PERIOD OF CHEMICAL TREATMENT ON PORCINE PERICARDIUM2019

    • Author(s)
      Inoue T, Kanda K, Yamanami M, Kami D, Gojo S, Yaku H.
    • Organizer
      the Combined International Symposium for Applied Cardiovascular Biology and Vascular Tissue Engineering (ISACB+ISVTE 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EFFECTS OF CHEMICAL TREATMENTS ON MECHANICAL PROPERTIES OF IN VIVO TISSUE ENGINEERED VASCULAR GRAFTS2019

    • Author(s)
      Inoue T, Kanda K, Yamanami M, Kami D, Gojo S, Yaku H.
    • Organizer
      the Combined International Symposium for Applied Cardiovascular Biology and Vascular Tissue Engineering (ISACB+ISVTE 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DEVELOPMENT OF DECELLULARIZED IN VIVO TISSUE ENGINEERED VASCULAR GRAFTS FOR XENOGENEIC OR ALLOGENEIC IMPLANTATION2019

    • Author(s)
      Yamanami M, Kanda K, Morimoto K, Inoue T, Watanabe T, Sakai O, Kami D, Gojo S, Yaku H.
    • Organizer
      the Combined International Symposium for Applied Cardiovascular Biology and Vascular Tissue Engineering (ISACB+ISVTE 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EFFECTS OF SHORT PERIOD OF CHEMICAL MODIFICATION ON PORCINE PERICARDIUM2019

    • Author(s)
      Inoue T, Kanda K, Yamanami M, Kami D, Gojo S, Yaku H.
    • Organizer
      the XLVI ESAO (the European Society for Artificial Organs) 2019 Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MODIFICATIONS OF MECHANICAL PROPERTIES OF IN VIVO TISSUE ENGINEERED VASCULAR TISSUES BY SHORT PERIOD OF CHEMICAL TREATMENTS2019

    • Author(s)
      Inoue T, Kanda K, Yamanami M, Kami D, Gojo S, Yaku H.
    • Organizer
      the XLVI ESAO (the European Society for Artificial Organs) 2019 Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] APPLICATION OF IN VIVO TISSUE ENGINEERED DECELLULARIZED CONNECTIVE TISSUE FOR CARDIOVASCULAR GRAFTS2019

    • Author(s)
      Yamanami M, Kanda K, Morimoto K, Inoue T, Watanabe T, Sakai O, Kami D, Gojo S, Yaku H.
    • Organizer
      the XLVI ESAO (the European Society for Artificial Organs) 2019 Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IN VIVO TISSUE ENGINEERED VASCULAR GRAFTS ADAPTABLE TO AV SHUNTS2019

    • Author(s)
      Kanda K, Yamanami M, Inoue T, Watanabe T, Sakai O, Kami D, Gojo S, Yaku H.
    • Organizer
      the XLVI ESAO (the European Society for Artificial Organs) 2019 Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of in vivo tissue engineered decellularized connective tissue for tubular vascular grafts and vascular patches2019

    • Author(s)
      Yamanami M, Kanda K, Morimoto K, Inoue T, Watanabe T, Sakai O, Kami D, Gojo S, Yaku H.
    • Organizer
      the 8th Meeting of the International Federation for Artificial Organs (IFAO 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of ethanol and glutaraldehyde treatments on mechanical properties of porcine pericardium2019

    • Author(s)
      Inoue T, Kanda K, Yamanami M, Kami D, Gojo S, Yaku H.
    • Organizer
      the 8th Meeting of the International Federation for Artificial Organs (IFAO 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体内組織工学による代用血管開発への取り組みとよろず相談所での面談2019

    • Author(s)
      神田圭一、山南将志、井上知也、坂井修、上大介、五條理志、夜久均
    • Organizer
      第57回 日本人工臓器学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 患者体内で作成する自家結合組織代用血管臨床開始後の応用拡大に向けた取り組みについて2019

    • Author(s)
      神田圭一、山南将志、井上知也、坂井修、上大介、五條理志、夜久均
    • Organizer
      第57回 日本人工臓器学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] エタノール・グルタールアルデヒド処理による生体内組織工学代用血管の物理特性変化2019

    • Author(s)
      井上 知也,神田 圭一,山南 将志,渡辺 太治,坂井 修,上 大介,五條 理志,夜久 均
    • Organizer
      第49回日本心臓血管外科学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 化学処理による自家結合組織代用血管の物性変化2019

    • Author(s)
      井上 知也,神田 圭一,山南 将志,渡辺 太治,上 大介,五條 理志,夜久 均
    • Organizer
      第18回日本心臓血管外科再生治療研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] In vivo tissue engineeringにより作製した異種・同種結合組織膜の血管移植片への応用2019

    • Author(s)
      山南 将志,神田 圭一,井上 知也,渡辺 太治,坂井 修,上 大介,五條 理志,夜久 均
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] エタノールおよびグルタールアルデヒド処理が生体内組織工学代用血管の物理特性に及ぼす影響2019

    • Author(s)
      井上 知也,神田 圭一,山南 将志,渡辺 太治,坂井 修,上 大介,五條 理志,夜久 均
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 生体内組織工学による結合組織管の臨床応用拡大に向けての取り組み2019

    • Author(s)
      神田 圭一,山南 将志,井上 知也,上 大介,五條 理志,夜久 均,渡辺 太治
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of tissue engineered decellularized connective tissue membrane for allogeneic arterial patch implantation2018

    • Author(s)
      Yamanami Masashi,Kanda Keiichi,Morimoto Kazuki,Inoue Tomoya,Watanabe Taiji,Sakai Osamu,Kami Daisuke,Gojo Satoshi,Yaku Hitoshi
    • Organizer
      The 5th Tissue Engineering and Regenerative Medicine International Society World Congress (TERMIS-WC 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Application of tissue engineered decellularized connective tissue membrane for allogeneic arterial patch implantation2018

    • Author(s)
      Yamanami Masashi,Kanda Keiichi,Morimoto Kazuki,Inoue Tomoya,Watanabe Taiji,Sakai Osamu,Kami Daisuke,Gojo Satoshi,Yaku Hitoshi
    • Organizer
      The 45th Annual Congress of the European Society for Artificial Organs (ESAO 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Improbement of the durability and reliability of in vivo tissue engineered vascular tissues by chemical modification2018

    • Author(s)
      Inoue Tomoya,Kanda Keiichi,Yamanami Masashi,Watanabe Taiji,Sakai Osamu,Yaku Hitoshi
    • Organizer
      The 45th Annual Congress of the European Society for Artificial Organs (ESAO 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of in vivo tissue engineered decellularized connective tissue membrane for allogeneic cardiovascular grafts2018

    • Author(s)
      Yamanami Masashi,Kanda Keiichi,Morimoto Kazuki,Inoue Tomoya,Watanabe Taiji,Sakai Osamu,Kami Daisuke,Gojo Satoshi,Yaku Hitoshi
    • Organizer
      The 16th International Society for Applied Cardiovascular Biology Meeting (ISACB 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脱細胞化同種結合組織膜の血管移植片への応用2018

    • Author(s)
      山南 将志,神田 圭一,森本 和樹,井上 知也,渡辺 太治,坂井 修,上 大介,五條 理志,夜久 均
    • Organizer
      第56回日本人工臓器学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 化学処理による結合組織管(バイオチューブ)の物理特性変化に対する検討2018

    • Author(s)
      井上 知也,神田 圭一,山南 将志,渡辺 太治,坂井 修,上 大介,五條 理志,夜久 均
    • Organizer
      第56回日本人工臓器学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 組織工学的手法で作製した脱細胞化結合組織膜の動脈パッチ移植への応用2018

    • Author(s)
      山南 将志、神田 圭一、森本 和樹、井上 知也、渡辺 太治、坂井 修、上 大介、五條 理志、夜久 均
    • Organizer
      第48回日本心臓血管外科学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脱細胞化生体由来結合組織膜の動脈パッチ移植への応用2018

    • Author(s)
      山南 将志、神田 圭一、森本 和樹、井上 知也、渡辺 太治、坂井 修、上 大介、五條 理志、夜久 均
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] DEVELOPMENT OF IN VIVO TISSUE ENGINEERED XENOGENEIC VASCULAR GRAFTS2017

    • Author(s)
      Yamanami M, Kawasaki T, Kami D, Watanabe T, Kanda K, Gojo S, Yaku H
    • Organizer
      The Third International Symposium on Vascular Tissue Engineering
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The Development of Xenogeneic, Self-Organizing Small-Caliber Vascular Grafts2017

    • Author(s)
      Yamanami M, Kawasaki T, Kami D, Watanabe T, Kanda K, Gojo S, Yaku H
    • Organizer
      European Chapter Meeting of the Tissue Engineering and Regenerative Medicine International Society 2017 (TERMIS-EU 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Application of the xenogeneic decellularized tube matrix produced by in vivo tissue engineering to the ‘off-the-shelf’ small-caliber vascular graft2017

    • Author(s)
      Yamanami M, Kawasaki T, Kami D, Watanabe T, Kanda K, Gojo S, Yaku H
    • Organizer
      44th Annual Congress of the European Society for Artificial Organs (ESAO 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] いつでも使用可能な異種由来自己再生型小口径代用血管『バイオチューブ・マトリックス』の開発2016

    • Author(s)
      山南将志、河崎貴宣、上大介、渡辺太治、神田圭一、五條理志、夜久均
    • Organizer
      第54回日本人工臓器学会大会
    • Place of Presentation
      鳥取県米子市
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
  • [Presentation] The Development of Xenogenic, Self-Organizing Small-Diameter Vascular Graft Using "Biotube Matrix"2016

    • Author(s)
      Yamanami M, Kawasaki T, Kami D, Watanabe T, Kanda K, Gojo S, Yaku H
    • Organizer
      XLIII Annual Congress of the European Society for Artificial Organs
    • Place of Presentation
      ワルシャワ、ポーランド
    • Year and Date
      2016-09-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 『バイオチューブ・マトリックス』を活用した異種由来自己再生型小口径代用血管の開発2016

    • Author(s)
      山南将志、河崎貴宣、上大介、渡辺太治、神田圭一、五條理志、夜久均
    • Organizer
      第44回日本血管外科学会学術集会
    • Place of Presentation
      東京都港区
    • Year and Date
      2016-05-26
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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