次世代型自家組織由来心臓弁グラフト（バイオバルブ）の開発研究

2015 Fiscal Year Annual Research Report

• Project/Area Number: 15H04940
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: 武輪 能明 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (20332405)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 心臓弁膜症 / 人工弁 / 自家組織 / 組織工学 / 再生医療

Outline of Annual Research Achievements

われわれが開発した自己組織由来心血管グラフト（バイオバルブ）の中で、通常の開心術用人工弁、大動脈根部全置換術に使用可能なFull root type、それに経カテーテル的挿入術に使用可能なステント付き人工弁（バイオバルブステント）について、基本性能（人工弁の耐久性、抗血栓性、流体力学的性能）および長期性能の検討を行った。その結果急性実験にて、いずれのタイプのバイオバルブも、生体元々の弁に比べて同等以上の耐久性、流体力学的性能を示した。また、慢性実験による長期性能評価でも、良好な抗血栓性と、耐久性を示した。
また、小児へのバイオバルブ及びバイオチューブの応用を想定した、成長性の検討もヤギ成長モデルを用いて行った。その結果、体幹の成長に応じてバイオチューブも成長する傾向が見られ、バイタルグラフトとして機能する可能性が示された。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

当初より、平成２７年度から２８年度にかけて、1）バイオバルブステントの大動物を用いた、長期性能評価2）通常の開心術
用人工弁の大動物を用いた、急性実験による基本性能および長期性能評価、3）ヤギ成長モデルを用いたバイオチューブの成長性の検討を行うこととしており、概ね目標を達成している。

Strategy for Future Research Activity

平成２８年度は、２７年度と同様に、1）バイオバルブステントの大動物を用いた、長期性能評価2）通常の開心術用人工弁の大動物を用いた、急性実験による基本性能および長期性能評価、3）ヤギ成長モデルを用いたバイオチューブの成長性の検討を行い、その例数を増やし実現可能性を評価する。

Research Products

• [Journal Article] Mechanical properties of human autologous tubular connective tissues(human biotubes) obtained from patients undergoing peritoneal dialysis (2016)
  • Author(s): Yasuhide Nakayama, Yoshiyuki Kaneko, Yoshiaki Takewa Y, Noriko Okumura
  • Journal Title: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B: APPLIED MATERIALS Volume: 104 Pages: 1-10
  • DOI: 10.1002/jbm.b.33495
  • Peer Reviewed
• [Journal Article] Development of self-expanding valved stents with autologous tubular leaflet tissues for transcatheter valve implantation (2015)
  • Author(s): Marina Funayama, Hirohito Sumikura, Yoshiaki Takewa, Eisuke Tatsumi, Yasuhide Nakayama
  • Journal Title: JOURNAL OF ARTIFICIAL ORGANS Volume: 18 Pages: 228-235
  • DOI: 10.1007/s10047-015-0820-6
  • Peer Reviewed
• [Journal Article] In vitro hydrodynamic evaluation of a biovalve with stent (tubular leaflet type) for transcatheter pulmonary valve implantation (2015)
  • Author(s): Hirohito Sumikura, Yasuhide Nakayama, Kentaro Ohnuma, Satoru Kishimoto, Yoshiaki Takewa, Eisuke Tatsumi
  • Journal Title: JOURNAL OF ARTIFICIAL ORGANS Volume: 18 Pages: 307-314
  • DOI: 10.1007/s10047-015-0851-z
  • Peer Reviewed
• [Journal Article] Sutureless aortic valve replacement using a novel autologous tissue heart valve with stent (stent biovalve): proof of concept (2015)
  • Author(s): Satoru Kishimoto, Yoshiaki Takewa, Yasuhide Nakayama, Kazuma Date, Hirohito Sumikura, Takeshi Moriwaki, Motonobu Nishimura, Eisuke
  • Journal Title: JOURNAL OF ARTIFICIAL ORGANS Volume: 18 Pages: 185-190
  • DOI: 10.1007/s10047-015-0817-1
  • Peer Reviewed
• [Journal Article] In situ observation and enhancement of leaflet tissue formation in bioprosthetic "biovalve" (2015)
  • Author(s): Marina Funayama, Yoshiaki Takewa, Tomonori Oie, Yuichi Matsui, Eisuke Tatsumi, Yasuhide Nakayama
  • Journal Title: JOURNAL OF ARTIFICIAL ORGANS Volume: 18 Pages: 40-47
  • DOI: 10.1007/s10047-014-0793-x
  • Peer Reviewed
• [Journal Article] In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding (2015)
  • Author(s): Yasuhide Nakayama, Yoshiaki Takewa, Hirohito Sumikura, Masashi Yamanami, Yuichi Matsui, Tomonori Oie, Yuichiro Kishimoto, Mamoru Arakawa, Kentaro Ohmuma, Tsutomu Tajikawa, Keiichi Kanda, EisukeTatsumi
  • Journal Title: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B: APPLIED MATERIALS Volume: 103 Pages: 1-11
  • DOI: 10.1002/jbm.b.33186
  • Peer Reviewed
• [Presentation] Development of a novel autologous heart valve(biovalve) with in-body tissue engineering method (2015)
  • Author(s): Takewa Y
  • Organizer: 2015 European International Society for Applied Cardiovascular biology Meeting
  • Place of Presentation: ニュルンベルグ
  • Year and Date: 2015-12-03 – 2015-12-05
  • Int'l Joint Research
• [Presentation] 将来有望な自己組織からなる生体弁の開発研究 (2015)
  • Author(s): 武輪能明，中山泰秀，内藤敬嗣，住倉博仁，竹下大輔，飯塚 慶，田中孝晴，妙中義之，巽 英介
  • Organizer: 日本人工臓器学会大会 (53）
  • Place of Presentation: 東京
  • Year and Date: 2015-11-19 – 2015-11-21
• [Presentation] 自己組織生体材料（バイオシート）は弁葉代用材料としての自己心膜を超えるか？バイオバルブの将来展望を見据えた取り組み (2015)
  • Author(s): 中山泰秀，宮本伸二，岡本啓太郎，和田朋之，森脇健司，武輪能明，巽 英介
  • Organizer: 日本人工臓器学会大会 (53）
  • Place of Presentation: 東京
  • Year and Date: 2015-11-19 – 2015-11-21
• [Presentation] A novel versatile bioprosthetic valve made by autologous tissues maintaining growth potential (2015)
  • Author(s): Takewa Y, Nakayama Y, Sumikura H, Naito N, Iizuka K, Furukoshi M, Tanaka T, Tatsumi E
  • Organizer: American Heart Association Scientific Sessions 2015
  • Place of Presentation: オーランド
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Development of in vivo, tissue-engineered, autologous, 3D heart valvular tissue, type SC biovalve with excellent mechanical properties, valvular functions, and in vivo performances (2015)
  • Author(s): Nakayama Y, Takewa Y, Moriwaki T, Sumikura H, Miyamoto S, Funayama M, Furukoshi M, Tatsumi E
  • Organizer: American Heart Association Scientific Sessions 2015
  • Place of Presentation: オーランド
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Improvement and evaluation of biovalve with stent for transcatheter pulmonary valve implantation (2015)
  • Author(s): Sumikura H, Nakayama Y, Ohnuma K, Takewa Y, Tatsumi E
  • Organizer: Annual European Society for Artificial Organs Congress
  • Place of Presentation: ルーベン
  • Year and Date: 2015-09-02 – 2015-09-05
  • Int'l Joint Research
• [Presentation] Development of a tailor made valve with autologous tissue (2015)
  • Author(s): Takewa Y, Nakayama Y, Sumikura H, Naito N, Kanada K, Tajikawa T, Tanaka T, Tatsumi E
  • Organizer: Annual European Society for Artificial Organs Congress
  • Place of Presentation: ルーベン
  • Year and Date: 2015-09-02 – 2015-09-05
  • Int'l Joint Research
• [Presentation] A tailor made valve surgery with a novel autologous bioprosthesis (2015)
  • Author(s): Takewa Y, Nakayama Y, Sumikura H, Naito N, Kanada K, Tajikawa T, Tanaka T, Tatsumi E
  • Organizer: European Society of Cardiology Congress 2015
  • Place of Presentation: ロンドン
  • Year and Date: 2015-08-29 – 2015-09-02
  • Int'l Joint Research
• [Presentation] In-body tissue engineered heart valve (biovalve) can be engrafted as vital tissues (2015)
  • Author(s): Takewa Y, Nakayama Y, Naito N, Sumikura H, Kanda K, Tajikawa T, Tatsumi E, Tanaka T
  • Organizer: American Society for Artificial Internal Organs
  • Place of Presentation: シカゴ
  • Year and Date: 2015-05-24 – 2015-05-27
  • Int'l Joint Research
• [Presentation] Long term evaluation of a novel autologous tissue engineered valve substitute(biovalve) (2015)
  • Author(s): Takewa Y, Nakayama Y, Kishimoto S, Naito N, Furukoshi M, Kanda K, Tajikawa T, Tatsumi E
  • Organizer: The Heart Valve Society Annual Meeting
  • Place of Presentation: モナコ
  • Year and Date: 2015-05-07 – 2015-05-09
  • Int'l Joint Research
• [Presentation] バイオバルブ開発における組織形成促進基材の開発 (2015)
  • Author(s): 住倉博仁
  • Organizer: 生体再生技術研究会 (11)
  • Place of Presentation: 東京
  • Year and Date: 2015-04-10 – 2015-04-11
• [Presentation] バイオバルブ開発の近況報告 (2015)
  • Author(s): 武輪能明
  • Organizer: 生体再生技術研究会 (11)
  • Place of Presentation: 東京
  • Year and Date: 2015-04-10 – 2015-04-11