Evaluation of a noble in-body tissue engineered heart valve (Biovalve) in the systemic circulation

2013 Fiscal Year Final Research Report

• Project/Area Number: 23659677
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: TAKEWA Yoshiaki 独立行政法人国立循環器病研究センター, 研究所, 室長 (20332405)
• Co-Investigator(Renkei-kenkyūsha): TATSUMI Eisuke 国立循環器病研究センター, 研究所, 部長 (00216996) ; NAKAYAMA Yasuhide 国立循環器病研究センター, 研究所, 部長 (50250262) ; UMEKI Akihide 国立循環器病研究センター, 研究所, 室員 (60596344)
• Research Collaborator: SUMIKURA Hirohito 国立循環器病研究センター, 研究所, 研究員 (20433998) ; OHNUMA Kentaro 国立循環器病研究センター, 研究所, 研究員 (50527992)
• Project Period (FY): 2011 – 2013
• Keywords: 自家組織 / 大動脈根部 / 組織工学 / 心臓弁 / 生体外組織工学 / バイオリアクター / 再生医療 / ステントバルブ

Research Abstract

An autologous valved conduit without any artificial support materials (Biovalve) was developed, using in-body tissue engineering. In this study, the potential of the Biovalve as an aortic valve was investigated in a goat model. Biovalves were prepared by 2-month embedding of molds in the subcutaneous space of goats. After removing the molds, Biovalves were made by perfectly autologous connective tissue. Biovalves were implanted as aortic valves using the apico-aortic bypass method for 2 months. Postoperative echocardiogram showed smooth movement of the leaflets with little regurgitation under the systemic circulation. At the sinus portions, marked elastic fibers were formed. The luminal surface was covered with thin pseudointima. In conclusion, completely autologous Biovalves with robust and elastic characteristics satisfied the higher requirements of systemic circulation in goats for 2 months.

Research Products

• [Journal Article] In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding (2014)
  • Author(s): Nakayama Y, Takewa Y, Sumikura H, Yamanami M, Matsui Y, Oie T, Kishimoto Y, Arakawa M, Ohmuma K, Tajikawa T, Kanda K, Tatsumi E
  • Journal Title: J Biomed Mater Res B Appl Biomater
  • DOI: 10.1002/jbm.b.33186.
  • Peer Reviewed
• [Journal Article] In vitro evaluation of a novel autologous aortic valve (biovalve) with a pulsatile circulation circuit (2014)
  • Author(s): Sumikura H, Nakayama Y, Ohnuma K, Takewa Y, Tatsumi E
  • Journal Title: Artif Organs. Artif Organs Volume: 38(4) Pages: 282-9
  • DOI: 10.1111/aor.12173.
  • Peer Reviewed
• [Journal Article] Preparation of an autologous heart valve with a stent (stent-biovalve) using the stent eversion method (2013)
  • Author(s): Mizuno T, Takewa Y, Sumikura H, Ohnuma K, Moriwaki T, Yamanami M, Oie T, Tatsumi E, Uechi M, Nakayama Y
  • Journal Title: J Biomed Mater Res B Appl Biomater
  • DOI: 10.1002/jbm.b.33086.
  • Peer Reviewed
• [Journal Article] In vivo evaluation of an in-body, tissue-engineered, completely autologous valved conduit (biovalve type VI) as an aortic valve in a goat model (2013)
  • Author(s): Takewa Y, Yamanami M, Kishimoto Y, Arakawa M, Kanda K, Matsui Y, Oie T, Ishibashi-Ueda H, Tajikawa T, Ohba K, Yaku H, Taenaka Y, Tatsumi E, Nakayama Y
  • Journal Title: J Artif Organs Volume: 6(2) Pages: 176-84
  • DOI: 10.1007/s10047-012-0679-8.
  • Peer Reviewed
• [Presentation] 自己組織からなる心臓弁(Biovalve) の開発 (2014)
  • Author(s): 武輪能明、中山康秀、岸本 諭、熱田祐一、伊達数馬、住倉博仁、広風らでぃ、神田圭一、田地川勉、田中孝晴、妙中義之、巽 英介
  • Organizer: 日本再生医療学会総会 (13)
  • Place of Presentation: 京都
  • Year and Date: 20140304-06
• [Presentation] 組織工学的に皮下で作成した自家組織由来心臓弁(Biovalve)の開発 (2014)
  • Author(s): 武輪能明、中山康秀、岸本 諭、熱田祐一、伊達数馬、神田圭一、広風らでぃ、妙中義之、巽 英介
  • Organizer: 日本心臓血管外科学会学術集会(44)
  • Place of Presentation: 熊本
  • Year and Date: 20140219-21
• [Presentation] Long-term Evaluation of a Novel Autologous Valve Substitute (Biovalve) with a Stent for Transcatheter Implantation (2013)
  • Author(s): Takewa Y, Nakayama Y, Atsuta Y, Kishimoto S, Date K, Sumikura H, Yamanami M, Kanda K, , Tajikawa T, Tanaka T, Taenaka Y, Tatsumi E
  • Organizer: American Heart Association , Scientific Sessions 2013
  • Place of Presentation: Dallas
  • Year and Date: 20131116-20
• [Presentation] 自己組織からなる心臓人工弁 Biovalve の開発 (2013)
  • Author(s): 武輪能明、中山泰秀、山南将志、熱田祐一、岸本 諭、伊達数馬、住倉博仁、大沼健太郎、水野荘司、神田圭一、田地川 勉、田中孝晴、妙中義之、巽 英介
  • Organizer: 日本人工臓器学会大会 (51)
  • Place of Presentation: 横浜
  • Year and Date: 20130927-29
• [Presentation] 3D プリンターの医療分野での活用 : バイオバルブ開発の3D 的発展 (2013)
  • Author(s): 中山泰秀、武輪能明、上地正実、神田圭一、田地川勉、大家智憲、大野正純
  • Organizer: 日本人工臓器学会大会 (51), International Federation for Artificial Organs (5)
  • Place of Presentation: 横浜
  • Year and Date: 20130927-29
• [Presentation] 血液透析用動静脈瘻作製後の静脈閉塞モデルにおける in situ バイオチューブbypass (2013)
  • Author(s): 水野荘司、川尻英長、金子嘉志、武輪能明、中山泰秀
  • Organizer: 日本人工臓器学会大会 (51), International Federation for Artificial Organs (5)
  • Place of Presentation: 横浜
  • Year and Date: 20130927-29
• [Presentation] ヒト体内で形成されたバイオチューブの物性評価と生体内機能評価 (2013)
  • Author(s): 中山泰秀、水野荘司、山南将志、武輪能明、金子嘉志、奥村紀子、花田 繁、巽 英介
  • Organizer: 日本人工臓器学会大会 (51), International Federation for Artificial Organs (5)
  • Place of Presentation: 横浜
  • Year and Date: 20130927-29
• [Presentation] Evaluation of novel autologous heart valve (Biovalve Stent) for transcatheter aortic valve implantation (2013)
  • Author(s): Takewa Y, Kanada K, Nakayama Y, Sumikura H, Taenaka Y, Tajikawa T, Tatsumi E, Yamanami M
  • Organizer: European Society for Artificial Organs (40)
  • Place of Presentation: Glasgow
  • Year and Date: 20130911-14
• [Presentation] Can human biotubes be used as artificial vascular grafts? (2013)
  • Author(s): Nakayama Y, Takewa Y, Kaneko T, Yamanami M, Mizuno T, Kwajiri H,Okumura N, Hanada S, Kanda K, Tatsumi E
  • Organizer: European Society for Artificial Organs (40)
  • Place of Presentation: Glasgow
  • Year and Date: 20130911-14
• [Presentation] Novel stent eversion method for the preparation of autologous valve with stent (Stent-Biovalve) (2013)
  • Author(s): Mizuno T, Takewa Y, Sumikura H, Omura T, Tsujinaka T, Yamanami M, Tatsumi E, Nakayama Y
  • Organizer: European Society for Artificial Organs (40)
  • Place of Presentation: Glasgow
  • Year and Date: 20130911-14
• [Presentation] Development of a novel autologous valve with stent (Biovalave stent) for TAVI (2013)
  • Author(s): Takewa Y, Nakayama Y, Arakawa M, Yamanami M, Ohnuma K, Sumikura H, Tajikawa T, Kanada K, Taenaka Y, Tatsumi E
  • Organizer: Heart Valve Society of America 7th Biennial congress
  • Place of Presentation: Venice
  • Year and Date: 20130622-25
• [Presentation] Development of a novel autologous valve with a stent (Biovalve stent) for transcatheter implantation (2013)
  • Author(s): Takewa Y, Nakayama Y, Arakawa M, Yamanami M, Kishimoto S, Atsuta Y, Ohnuma K, Sumikura H, Mizuno T, Kanda K, Tajikawa T, Taenaka Y, Tatsumi E
  • Organizer: American Society for Artificial Internal Organs (59)
  • Place of Presentation: Chicago
  • Year and Date: 20130612-15
• [Presentation] 自己組織心臓代用弁(バイオバルブ)の生体外機能評価 (2013)
  • Author(s): 住倉博仁、中山泰秀、大沼健太郎、武輪能明、巽 英介
  • Organizer: 日本バイオレオロジー学会年会 (36)
  • Place of Presentation: 福岡市
  • Year and Date: 20130606-08
• [Presentation] 反転型ステント付きバイオバルブの開発 : 作製方法の確実性の獲得をめざして (2013)
  • Author(s): 水野壮司、山南将志、森脇健司、住倉博仁、大沼健太郎、武輪能明、巽 英介、上地正実、中山泰秀
  • Organizer: 日本再生医療学会総会(12)
  • Place of Presentation: 横浜市
  • Year and Date: 20130321-23
• [Presentation] ヒトバイオチューブの人工血管としての可能性 (2013)
  • Author(s): 中山泰秀、武輪能明、金子嘉志、奥村紀子
  • Organizer: 日本再生医療学会総会 (12)
  • Place of Presentation: 横浜市
  • Year and Date: 20130321-23
• [Presentation] 自己組織からなる TAVI 用 Stent 付き心臓弁 (Biovalve Stent) の開発 : 動物実験評価 (2012)
  • Author(s): 武輪能明、中山泰秀、岸本祐一郎、荒川 衛、山南将志、住倉博仁、大沼健太郎、熱田祐一、藤井 豊、水野壮司、松井悠一、神田圭一、田地川勉、妙中義之、巽英介
  • Organizer: 日本人工臓器学会大会 (50)
  • Place of Presentation: 福岡市
  • Year and Date: 20121122-24
• [Presentation] バイオバルブ大動脈弁 ( Type VII ) の開発 (2012)
  • Author(s): 中山泰秀、武輪能明、松井悠一、岸本祐一郎、荒川 衛、住倉博仁、大沼健太郎、山南将志、水野壮司、田地川勉、神田圭一、巽 英介
  • Organizer: 日本人工臓器学会大会 (50)
  • Place of Presentation: 福岡市
  • Year and Date: 20121122-24
• [Presentation] バイオバルブ心臓弁の拍動流回路を用いた生体外機能・耐久性評価 (2012)
  • Author(s): 住倉博仁、中山泰秀、武輪能明、大沼健太郎、巽 英介
  • Organizer: 日本人工臓器学会大会 (50)
  • Place of Presentation: 福岡市
  • Year and Date: 20121122-24
• [Presentation] Successful implantation of a completely autologous aortic valve with a stent (Biovalve stent) by transcatheter aortic valve implantation (TAVI) (2012)
  • Author(s): Takewa Y, Nakayama Y, Yamanami M, Kishimoto Y, Arakawa M, Ohnuma K, Sumikura H, Kanda K, Matsui Y, Taenaka Y, Tatsumi E
  • Organizer: American Heart Association, Scientific Sessions 2012
  • Place of Presentation: Los Angeles (USA)
  • Year and Date: 20121103-07
• [Presentation] In vitro and in vivo performance of a completely autologous aortic valued conduit (BIOVALVE Type VII) prepared by in body tissue architecture technology using a novel separable mold (2012)
  • Author(s): Nakayama Y, Takewa Y, Sumikura H, Matsui Y, Yamanami M, Kishimoto Y, Arakawa M, Ohnuma K, Mizuno T, Oie T, Kanda K, Tatsumi E
  • Organizer: American Heart Association, Scientific Sessions 2012
  • Place of Presentation: Los Angeles (USA)
  • Year and Date: 20121103-07
• [Presentation] 組織工学的に皮下で作成した自家組織大動脈弁 (Biovalve) のTAVI を用いた治療の可能性 (2012)
  • Author(s): 武輪能明、中山泰秀、岸本祐一郎、荒川 衛、山南将志、住倉博仁、大沼健太郎、藤井 豊、松井悠一、神田圭一、夜久 均、田地川 勉、大場謙吉、妙中義之、巽 英介
  • Organizer: 日本胸部外科学会定期学術集会 (65)
  • Place of Presentation: 福岡市
  • Year and Date: 20121017-20
• [Presentation] Novel autologous heart valve (Biovalve Stent) for transcatheter aortic valve implantation (2012)
  • Author(s): Takewa Y, Nakayama Y, Matsui Y, Yamanami M, Kanda K, Tatsumi E
  • Organizer: European Society for Artificial Organs (36)
  • Place of Presentation: Rostock (Germany)
  • Year and Date: 20120926-29
• [Presentation] In vivo-tissue engineered autologous aortic valved conduits (Biovalves type VII) : preparation and revolution (2012)
  • Author(s): Nakayama Y, Takewa Y, Sumikura H, Matsui Y, Yamanami M, Kishimoto Y, Akagawa E, Okumura K, Tajikawa T, Kanda K, Taenaka Y, Tatsumi E
  • Organizer: European Society for Artificial Organs (36)
  • Place of Presentation: Rostock (Germany)
  • Year and Date: 20120926-29
• [Presentation] In vivo evaluation of a novel autologous valve with a stent (biovalve stent) for transcatheter aortic valve implantation (TAVI) (2012)
  • Author(s): Takewa Y, Nakayama Y, Matsui Y, Yamanami M, Kishimoto Y, Arakawa M, Ohnuma K, Sumikura H, Kanda K, Yaku, H, Taenaka Y, Tatsumi E
  • Organizer: American Society for Artificial Internal Organs (58)
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 20120613-16
• [Presentation] In vitro evaluation of a novel autologous aortic valve (BIOVALVE) with a special pulsatile circulation circuit (2012)
  • Author(s): Sumikura H, Nakayama Y, Ohnuma K, Takewa Y, Tatsumi E
  • Organizer: American Society for Artificial Internal Organs (58)
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 20120613-16
• [Presentation] 患者の体内で自家移植用臓器を作成し、移植後急速な再生組織構築を誘導する『生体内組織形成技術』の開発 (2012)
  • Author(s): 神田圭一、山南将志、渡辺太治、田地川 努、大場謙吉、武輪能明、巽 英介、上地正実、夜久均、中山泰秀
  • Organizer: 日本再生医療学会総会 (11)
  • Place of Presentation: 横浜市
  • Year and Date: 20120612-14
• [Presentation] 中山泰秀、神田圭一、武輪能明、上地正実、渡辺太治、山南将志 (2012)
  • Author(s): 生体内組織形成術 : 自分の移植物を自分の体内で作れる新技術
  • Organizer: 日本再生医療学会総会 (11)
  • Place of Presentation: 横浜市
  • Year and Date: 20120612-14
• [Presentation] バイオバルブ心臓弁の生体外機能・耐久性評価 (2012)
  • Author(s): 中山泰秀、住倉博仁、大沼健太郎、武輪能明、巽 英介
  • Organizer: 日本再生医療学会総会 (11)
  • Place of Presentation: 横浜市
  • Year and Date: 20120612-14
• [Presentation] バイオバルブ心臓弁の生体内形成過程のカプセル内視鏡観察 (2012)
  • Author(s): 中山泰秀、武輪能明、大家智憲、山南将志、神田圭一、松井悠一、田地川 勉、大場謙吉、妙中義之、巽 英介
  • Organizer: 日本再生医療学会総会 (11)
  • Place of Presentation: 横浜市
  • Year and Date: 20120612-14
• [Presentation] 組織工学的に皮下で作成した心臓弁(BIOVALVE)の左心系自家移植による評価 (2012)
  • Author(s): 武輪能明、中山泰秀、岸本祐一郎、荒川 衛、山南将志、住倉博仁、大沼健太郎、藤井 豊、松井悠一、神田圭一、夜久 均、田地川 勉、大場謙吉、妙中義之、巽 英介
  • Organizer: 日本再生医療学会総会 (11)
  • Place of Presentation: 横浜市
  • Year and Date: 20120612-14
• [Presentation] 生体内組織形成技術による循環器系再生医療デバイスの開発 (2012)
  • Author(s): 山南将志、渡辺太治、神田圭一、夜久 均、上地正実、武輪能明、巽 英介、中山泰秀
  • Organizer: 日本再生医療学会総会 (11)
  • Place of Presentation: 横浜市
  • Year and Date: 20120612-14
• [Presentation] Development of in-body tissue-engineered, completely autologous valve (BIOVALVE) (2012)
  • Author(s): Takewa Y, Nakayama Y, Yamanami M, Kishimoto Y, Arakawa M, Matsui Y, Kanda K, Yaku H, Tajikawa T, Ohba K, Taenaka Y, Tatsumi E
  • Organizer: 5th biennial conference on Heart valve biology and tissue engineering
  • Place of Presentation: Myconos island (Greece)
  • Year and Date: 20120518-20
• [Presentation] 生体内組織形成技術で作成した心臓弁付Conduit (BIOVALVE)の大動脈系自家移植実験 (2012)
  • Author(s): 山南将志、武輪能明、岸本祐一郎、荒川 衛、住倉博仁、大沼健太郎、松井悠一、渡辺太治、神田圭一、夜久 均、田地川勉、大場謙吉、妙中義之、巽 英介、中山泰秀
  • Organizer: 日本心臓血管外科学会学術総会(42)
  • Place of Presentation: 秋田市
  • Year and Date: 20120418-20
• [Presentation] 組織工学的に皮下で作成したStent 付き心臓弁 (Biovalve Stent) の経カテーテル的自家移植の試み (2012)
  • Author(s): 武輪能明、中山泰秀、山南将志、岸本祐一郎、荒川 衛、住倉博仁、大沼健太郎、熱田祐一、水野壮司、松井悠一、神田圭一、田地川 勉、Wieloch. R、妙中義之、巽 英介
  • Organizer: 日本再生医療学会総会 (12)
  • Place of Presentation: 横浜市
  • Year and Date: 20120321-23
• [Presentation] カプセル内視鏡内臓鋳型を用いた体内組織形成過程のin situ 観察 (2011)
  • Author(s): 中山泰秀、武輪能明、大家智憲、山南将志、松井悠一、田地川 勉、大場謙吉、神田圭一、夜久均、巽 英介、妙中義之
  • Organizer: 日本人工臓器学会大会 (49)
  • Place of Presentation: 東京
  • Year and Date: 2011-11-25
• [Presentation] 開口位バイオバルブ人工弁の組立式設計によるストレスフリー摘出 (Type VII) (2011)
  • Author(s): 松井悠一、山南将志、武輪能明、田地川 勉、大場謙吉、神田圭一、夜久 均、巽 英介、中山泰秀
  • Organizer: 日本人工臓器学会大会 (49)
  • Place of Presentation: 東京
  • Year and Date: 2011-11-25
• [Presentation] Successful aortic valve implantation using an in-Body tissue-engineered, completely autologous valved conduit (BIOVALVE) in a goat model (2011)
  • Author(s): Takewa Y, Nakayama Y, Yamanami M, Umeki A, Matsui Y, Kanda K, Yaku H, Tajikawa T, Ohba K, Taenaka Y, Tatsumi E
  • Organizer: Anerican Heart Association Scientific Sessions
  • Place of Presentation: オーランド(米国)
  • Year and Date: 2011-11-12
• [Presentation] In-body tissue-engineered and completely autologous aortic valved conduit (BIOVALVE) in a goat model (2011)
  • Author(s): Takewa Y, Nakayama Y, Yamanami M, Hanada S, Umeki A, Matsui Y, Kanda K, Yaku H, Tajikawa T, Ohba K, Taenaka Y, Tatsumi E
  • Place of Presentation: ポルト(ポルトガル)
  • Year and Date: 2011-10-09
• [Presentation] Architecture design of a novel separable mold to obtain autologous tissue heart valves "Biovalves" non-invasively (2011)
  • Author(s): Nakayama Y, Matsui Y, Yamanami M, Takewa Y, Tatsumi E, Taenaka Y, Oie T, Tajikawa T, Ohba K, Kanda K, Yaku H
  • Organizer: Joint ESAO-IFAO Congress (4)
  • Place of Presentation: ポルト(ポルトガル)
  • Year and Date: 2011-10-09
• [Presentation] Preparation of a completely autologous valved conduit with the open form of trileaflets (type VI BIOVALVE) (2011)
  • Author(s): Yamanami M, Yahata Y, Uechi M, Takewa Y, Shimakawa Y, Matsui Y, Tajikawa T, Ohba K, Kanda K, Yaku H, Tatsumi E, Nakayama Y
  • Organizer: Joint ESAO-IFAO Congress (4)
  • Place of Presentation: ポルト(ポルトガル)
  • Year and Date: 2011-10-09
• [Presentation] Development of an in-body tissue-engineered autologous aortic bioprosthesis (2011)
  • Author(s): Takewa Y, Nakayama Y, Yamanami M, Matsui Y, Kanda K, Yaku H, Tajikawa T, Ohba K, Taenaka Y, Tatsumi E
  • Organizer: Joint meeting of the society for heart valve disease & heart valve society of America
  • Place of Presentation: バルセロナ(スペイン)
  • Year and Date: 2011-06-25
• [Presentation] In vivo evaluation of an in-body tissue-engineered and completely autologous aortic valved conduit (bio-valve) in a goat model (2011)
  • Author(s): Takewa Y, Nakayama Y, Yamanami M, Hanada S,Umeki A, Matsui Y, Kanda K, Yaku H, Tajikawa T, Ohba K, Taenaka Y, Tatsumi E
  • Organizer: American Society for Artificial Internal Organs (57)
  • Place of Presentation: ワシントンDC(米国)
  • Year and Date: 2011-06-10
• [Presentation] 完全自己組織からなる心臓弁様組織体バイオバルブ(Type VI)の開発 : 開口形状での弁形成による弁機能の向上 (2011)
  • Author(s): 山並将志、矢羽田侑希、上地正実、武輪能明、島川祐司、松川悠一、田地川 勉、大場謙吉、神田圭一、夜久 均、巽 英介、中山泰秀
  • Organizer: 日本炎症・再生医学会 (32)
  • Place of Presentation: 京都
  • Year and Date: 2011-06-02
• [Presentation] バイオバルブの開発 : 作成用鋳型の変遷 (2011)
  • Author(s): 中山泰秀、松井悠一、山並将志、田地川 勉、大場謙吉、神田圭一、夜久 均、上地正実、武輪能明、巽 英介
  • Organizer: 日本炎症・再生医学会 (32)
  • Place of Presentation: 京都
  • Year and Date: 2011-06-02
• [Presentation] 組織学的に皮下で作製した心臓弁付きConduit(Biovalve)の左心系自家移植による評価 (2011)
  • Author(s): 武輪能明、中山泰秀、山南将志、花田 繁、齋藤友宏、梅木昭秀、松井悠一、神田圭一、夜久 均、田地川勉、大場謙吉、妙中義之、巽 英介
  • Organizer: 日本再生医療学会総会(10)
  • Place of Presentation: 東京
  • Year and Date: 2011-03-01
• [Patent(Industrial Property Rights)] ステント及びステント付き人工弁 (2013)
  • Inventor(s): 武輪能明、他4名
  • Industrial Property Rights Holder: 武輪能明、他4名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 12P618
  • Filing Date: 2013-01-24