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2013 Fiscal Year Annual Research Report

組織工学的に皮下で作製した心臓弁(バイオバルブ)の大動脈系自家移植による性能評価

Research Project

Project/Area Number 23659677
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

武輪 能明  独立行政法人国立循環器病研究センター, 研究所, 室長 (20332405)

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

我々が開発中のバイオバルブ人工弁は、高分子製鋳型を皮下に1~2ヶ月埋入することで自動的に形成される。これまでラットや兎の他、山羊や牛など大動物においても、皮下での作製が可能であることが示されている。
前年度の研究では、皮下より採取したバイオバルブ人工弁を体の体循環系に移植して、性能を評価した。また、現在臨床で使用され始めている経管的大動脈弁移植術(TAVI)への応用として、ステント付きバイオバルブの設計を行った。
今年度は、バイオバルブの体循環系での性能評価実験をさらに行った。また、TAVI用の鋳型をステントと共に生体内に埋入し、ステント付きバイオバルブが設計通り形成されるか確認した。
方法は、バイオバルブ鋳型を成ヤギ背部の皮下に埋入して8週間後摘出し、鋳型を抜去して得られたバイオバルブを用いて手術的に左心バイパス(Apico-aortic bypass)を作成し、動脈圧負荷がかかる状態で慢性的に性能を評価した。
その結果、最長8週目までは、バイパスグラフトの血流は良好でバイオバルブ弁葉の可動性も良く、顕著な狭窄や逆流もなく経過した。組織学的にも結合組織の中に細胞侵入が見られ、新生血管の構築も見られたことより、バイオバルブが、高圧系でも自己弁に近い性能を持って機能し得ることが示された。ただ、Apico-aortic bypassによる評価では、8週以上になると、心尖脱血管の部分で血栓形成を生じる例があり、長期評価は、別モデルで行う必要があると考えられた。
ステント付きバイオバルブについては、ステントとバイオバルブ鋳型を組み合わせた物を成ヤギ背部の皮下に埋入して8週間後摘出した。鋳型を取り除いた結果、ステントと強固に融合したバイオバルブが得られ、組織破壊を生じずにステントを収縮拡張出来ることが確認された。以上より、ステント付きバイオバルブ組織体が設計通り形成される事が確認できた。

  • Research Products

    (50 results)

All 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (43 results)

  • [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.

      Volume: 38(4) Pages: 282-9

    • DOI

      10.1111/aor.12173.

    • Peer Reviewed
  • [Journal Article] Novel control system to prevent right ventricular failure induced by rotary blood pump.2014

    • Author(s)
      Arakawa M, Nishimura T, Takewa Y, Umeki A, Ando M, Kishimoto Y, Fujii Y, Kyo S, Adachi H, Tatsumi E.
    • Journal Title

      J Artif Organs.

      Volume: Epub ahead of print Pages: 1-10

    • Peer Reviewed
  • [Journal Article] Alternation of left ventricular load by a continuous-flow left ventricular assist device with a native heart load control system in a chronic heart failure model.2014

    • Author(s)
      Arakawa M, Nishimura T, Takewa Y, Umeki A, Ando M, Adachi H, Tatsumi E.
    • Journal Title

      J Thorac Cardiovasc Surg.

      Volume: Epub ahead of print Pages: 1-10

    • DOI

      10.1016/j.jtcvs.2013.12.049.

    • Peer Reviewed
  • [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.

      Volume: Epub ahead of print] Pages: 1-10

    • DOI

      10.1002/jbm.b.33186.

    • Peer Reviewed
  • [Journal Article] Stimulating myocardial regeneration with periostin Peptide in large mammals improves function post-myocardial infarction but increases myocardial fibrosis.2013

    • Author(s)
      Ladage D, Yaniz-Galende E, Rapti K, Ishikawa K, Tilemann L, Shapiro S, Takewa Y, Muller-Ehmsen J, Schwarz M, Garcia MJ, Sanz J, Hajjar RJ, Kawase Y.
    • Journal Title

      PLoS One.

      Volume: 8(5) Pages: e59656 1-11

    • DOI

      10.1371/journal.pone.0059656.

    • Peer Reviewed
  • [Journal Article] Hyperoxic condition promotes an inflammatory response during cardiopulmonary bypass in a rat model.2013

    • Author(s)
      Fujii Y, Shirai M, Tsuchimochi H, Pearson JT, Takewa Y, Tatsumi E, Taenaka Y.
    • Journal Title

      Artif Organs.

      Volume: 37(12) Pages: 1034-40

    • DOI

      10.1111/aor.12125.

    • 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.

      Volume: Dec 9 Pages: 1-10

    • DOI

      10.1002/jbm.b.33086.

    • 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
      20140304-20140306
  • [Presentation] VVECMOを効率良く行うためのカニュレーション位置の検討2014

    • Author(s)
      東郷好美、武輪能明、熱田祐一、片桐伸将、藤井 豊、宮本裕治、巽 英介
    • Organizer
      日本経皮的心肺補助(PCPS)研究会 (23)
    • Place of Presentation
      京都
    • Year and Date
      20140301-20140301
  • [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
      20140219-20140221
  • [Presentation] Long-term Evaluation of a Novel Autologous Valve Substitute (Biovalve) with a Stent for Transcatheter Implantation2013

    • 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] 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] 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
      20130927-20130929
  • [Presentation] The effect or continuous-flow LVAD control with cardiac cycle synchronization2013

    • Author(s)
      Nishimura T, Takewa Y, Ando M, Umeki A, Arakawa M, Kishimoto Y, Date K, Tatsumi E
    • 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
      20130927-20130929
  • [Presentation] Long-term evaluation of a durable and thrombo-resistant ECMO system consisting of BIOCUBE6000 and SOFTLINE coated RATAFLOW2013

    • Author(s)
      Katagiri N, Tatsumi E, Takewa Y, Mizuno T, Tsukiya T, Atsuta Y, Kato Y, Taenaka Y
    • 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
      20130927-20130929
  • [Presentation] Hyperoxia condition promotes an inflammatory response during extracorporeal circulation in a rat model2013

    • Author(s)
      Fujii Y, Tatsumi E, Shirai M, Takewa Y, Taenaka Y
    • 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
      20130927-20130929
  • [Presentation] Pathological changes in cardio-pulmonary tissue of the goat following prolonged venoarterial ECMO2013

    • Author(s)
      Mizuno T, Katagiri N, Tsukiya T, Takewa Y, Tatsumi E
    • 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
      20130927-20130929
  • [Presentation] The safe program for a newly developed electrocardiogram-synchronized rotational speed control mode with continuous-flow left ventricular assist device2013

    • Author(s)
      Arakawa M, Nishimura T, Takewa Y, Umeki A, Ando M, Kishimoto Y, Kishimoto S, Fujii Y, Kyo S, Adachi H, Tatsumi E
    • 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
      20130927-20130929
  • [Presentation] A non-invasive assessment of cardiac function during continuous-flow LVAD support by HRV analysis2013

    • Author(s)
      Kishimoto S, Kishimoto Y, Ohnuma K, Arakawa M, Date K, Takewa Y, Nishimura M, Tatsumi E
    • 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
      20130927-20130929
  • [Presentation] The potentially of non-synchronized pulsatile mode with a rotary LVAD by a native heart load control system2013

    • Author(s)
      Date K, Arakawa M, Takewa Y, Nishimura T, Kishimoto S, Kishimoto Y, Umeki A, Ando M, Kyo S, Ono M, Tatsumi E
    • 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
      20130927-20130929
  • [Presentation] Assessment of the cannula exit site infection in two different configuration, porous material coverd vs non-coverd tube2013

    • Author(s)
      Mizuno T, Takewa Y, Tsukiya T, Yanagisono Y, Kobara, Taenaka Y, Tasumi E
    • 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
      20130927-20130929
  • [Presentation] In vitro paerformance of an miniaturised axial flow ventricular assist device2013

    • Author(s)
      Tsukiya T, Mizuno T, Hoshi H, Okubo T, Yamane T, Maruyama O, Takewa Y, Tatsumi E
    • 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
      20130927-20130929
  • [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
      20130927-20130929
  • [Presentation] 人工臓器開発における数値シミュレーションの利用と限界2013

    • Author(s)
      築谷朋典、水野敏秀、武輪能明、巽 英介、妙中義之
    • 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
      20130927-20130929
  • [Presentation] VVECMOを効率良く行うためのバイパス流量と送血位置の検討2013

    • Author(s)
      東郷好美、武輪能明、築谷朋典、水野敏秀、片桐伸将、熱田祐一、藤井 豊、岸本 諭、伊達数馬、住倉博仁、大沼健太郎、角田幸秀、宮本裕治、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
      20130927-20130929
  • [Presentation] 小児用国循型ニプロ社製拍動型補助人工心臓(Mサイズ)の4例の前臨床試験2013

    • Author(s)
      武輪能明、熱田祐一、岸本 諭、伊達数馬、柳園宜紀、一ノ瀬隆高紀、妙中義之、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
      20130927-20130929
  • [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 bypass2013

    • 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
      20130927-20130929
  • [Presentation] 空気圧駆動式ウエアラブル全人工心臓システムのための小型駆動装置の開発2013

    • Author(s)
      大沼健太郎、住倉博仁、本間章彦、築谷朋典、武輪能明、水野敏秀、向林 宏、小嶋孝一、片野一夫、妙中、義之、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
      20130927-20130929
  • [Presentation] In vitro evaluation of the hydrodynamically levitated centrifugal blood pump as a extracorporeal ventricular assist device2013

    • Author(s)
      Tsukiya T, Mizuno T, Takewa Y, Sumikura H, Ohnuma K, Hoshi H, Okubo T, Tatsumi E, Taenaka Y
    • Organizer
      International Society for Rotary Blood Pumps (21)
    • Place of Presentation
      横浜
    • Year and Date
      20130926-20130928
  • [Presentation] Longtime pulsatile control using a rotary blood pump with a newly developed electrocardiogram synchronized rotational speed control system2013

    • Author(s)
      Arakawa M, Nishimura T, Takewa Y, Umeki A, Ando M, Kishimoto Y, Kishimoto S, Yamazaki K, Kyo S, Adachi H, Tatsumi E
    • Organizer
      International Society for Rotary Blood Pumps (21)
    • Place of Presentation
      横浜
    • Year and Date
      20130926-20130928
  • [Presentation] The difference between front load and delay load in the pulsatile mode with a rotary LVAD by a native heart load control system2013

    • Author(s)
      Date K, Arakawa M, Takewa Y, Nishimura T, Kishimoto S, Kishimoto Y, Umeki A, Ando M, Kyo S, Ono M, Tatsumi E
    • Organizer
      International Society for Rotary Blood Pumps (21)
    • Place of Presentation
      横浜
    • Year and Date
      20130926-20130928
  • [Presentation] Evaluation of long-term durability of a T-NCVC coated ECMO system with GYRO pump for cardiopulmonary support use2013

    • Author(s)
      Katagiri N, Tatsumi E, Takewa Y, Mizuno T, Tsukiya T, Kobara D, Yanaginoso Y, Taenaka Y
    • Organizer
      International Society for Rotary Blood Pumps (21)
    • Place of Presentation
      横浜
    • Year and Date
      20130926-20130928
  • [Presentation] Useful operating method of veno-venous extracorporeal membrane oxygenation aiming for effective oxygenation and decarboxylation2013

    • Author(s)
      Togo K, Takewa Y, Tsukiya T, Mizuno T, Katagiri N, Atsuta Y, Fujii Y, Kishimoto S, Date K, Sumikura H, Ohnuma K, Kakuta Y, Miyamoto Y, Tatsumi E
    • Organizer
      International Society for Rotary Blood Pumps (21)
    • Place of Presentation
      横浜
    • Year and Date
      20130926-20130928
  • [Presentation] Evaluation of novel autologous heart valve (Biovalve Stent) for transcatheter aortic valve implantation2013

    • 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
      20130911-20130914
  • [Presentation] Useful operating method of veno-venous extracorporeal membrane oxygenation aiming for effective oxygenation2013

    • Author(s)
      Togo K, Atsuta Y, Fujii Y, Kakuta Y, Katagiri N, Kishimoto Y, Miyamoto T, Mizuno T, Ohnuma K, Sumikura H, Taenaka Y, Takewa Y, Tatsumi E, Tsukiya T
    • Organizer
      European Society for Artificial Organs (40)
    • Place of Presentation
      Glasgow
    • Year and Date
      20130911-20130914
  • [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 TAVI2013

    • 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] In vivo evaluation of the percutaneous site of VAD system2013

    • Author(s)
      Atsuta Y, Mizuno T, Takewa Y, Tsukiya T, Kakuta Y, Katagiri N, Ohnuma K, Sumikura H, Fujii Y, Arakawa M, Togo K, Kishimoto S, Tatsumi E
    • Organizer
      American Society for Artificial Internal Organs (59)
    • Place of Presentation
      Chicago
    • Year and Date
      20130612-20130615
  • [Presentation] Enchantment of the myocardial perfusion by a novel cardiac cycle-synchronized rotation control mode in a continuous-flow in chronic ischemic heart failure model2013

    • Author(s)
      Arakawa M, Nishimura T, Takewa Y, Umeki A, Ando M, Date K, Atsuta Y, Fujii Y, Kishimoto S, Kyo S, Adachi H, Tatsumi E
    • Organizer
      American Society for Artificial Internal Organs (59)
    • Place of Presentation
      Chicago
    • Year and Date
      20130612-20130615
  • [Presentation] Hydrogen gas suppresses systemic inflammatory response during cardiopulmonary bypass in a rat model2013

    • Author(s)
      Fujii Y, Tatsumi E, Shirai M, Takewa Y, Taenaka Y
    • Organizer
      American Society for Artificial Internal Organs (59)
    • Place of Presentation
      Chicago
    • Year and Date
      20130612-20130615
  • [Presentation] A proposal of flexible control algorithm for artificial heart based on stochastic method2013

    • Author(s)
      Ohnuma K, Sumikura H, Homma A, Tsukiya T, Mizuno T, Takewa Y, Akagawa E, Fukui Y, Tatsumi E
    • Organizer
      American Society for Artificial Internal Organs (59)
    • Place of Presentation
      Chicago
    • Year and Date
      20130612-20130615
  • [Presentation] In vitro and in vivo evaluation of a compact wearable pneumatic drive unit for a ventricular assist device2013

    • Author(s)
      Sumikura H, Homma A, Ohnuma K, Taenaka Y, Takewa Y, Mizuno T, Tsukiya T, Katagiri N, Kakuta Y, Mukaibayashi H, Katano K, Kojma K, Fukui Y, Tatsumi E
    • Organizer
      American Society for Artificial Internal Organs (59)
    • Place of Presentation
      Chicago
    • Year and Date
      20130612-20130615
  • [Presentation] Practical operating method of veno-venous extracorporeal membrane oxygenation aiming for effective oxygenation2013

    • Author(s)
      Togo K, Takewa Y, Mizuno T, Tsukiya T, Atsuta Y, Arakawa M, Kishinmoto S, Katagiri N, Kakuta Y, Fujii Y, Sumikura H, Ohnuma K, Taenaka Y, MiyamotoY, Tatsumi E
    • Organizer
      American Society for Artificial Internal Organs (59)
    • Place of Presentation
      Chicago
    • Year and Date
      20130612-20130615
  • [Presentation] Evaluation of long-term durability of an antithrombogenic-coated ECMO system with Gyro pump2013

    • Author(s)
      Katagiri N, Tatsumi E, Takewa Y, Mizuno T, Tsukiya T, Kobara D, Yanagisono Y, Taenaka Y
    • Organizer
      American Society for Artificial Internal Organs (59)
    • Place of Presentation
      Chicago
    • Year and Date
      20130612-20130615
  • [Presentation] Development of a novel autologous valve with a stent (Biovalve stent) for transcatheter implantation2013

    • 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)
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    • Year and Date
      20130612-15
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      水野敏秀、山岡哲二、築谷朋典、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
    • Year and Date
      20130606-20130608
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      藤井 豊、巽 英介、白井幹康、武輪能明、妙中義之
    • Organizer
      日本バイオレオロジー学会年会 (36)
    • Place of Presentation
      福岡
    • Year and Date
      20130606-20130608
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      大沼健太郎、本間章彦、住倉博仁、築谷朋典、武輪能明、水野敏秀、向林 宏、小嶋孝一、片野一夫、妙中義之
    • Organizer
      日本バイオレオロジー学会年会 (36)
    • Place of Presentation
      福岡
    • Year and Date
      20130606-20130608
  • [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
      20130606-20130608

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Published: 2015-05-28  

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