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Pulmonary artery enlargement for congenital heart disease using connective tissue membrane using in vivo tissue engineering

Research Project

Project/Area Number 19H03742
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55030:Cardiovascular surgery-related
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) 権代 竜郎  京都府立医科大学, 医学部附属病院, 専攻医 (00970906)
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)
山岸 正明  京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (40182422)
夜久 均  京都府立医科大学, その他部局等, 学長 (50295648)
井上 知也  京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (50405289)
小田 晋一郎  京都府立医科大学, 医学(系)研究科(研究院), 教授 (50529873)
田中 秀央  京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (60236619)
神田 圭一  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60295649)
田地川 勉  関西大学, システム理工学部, 准教授 (80351500)
五條 理志  京都府立医科大学, 医学(系)研究科(研究院), 教授 (90316745)
川尻 英長  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40515235)
上 大介  京都府立医科大学, 医学(系)研究科(研究院), 講師 (80415588)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2023: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords血管移植片 / 人工血管 / 組織工学 / 結合組織 / 脱細胞 / 先天性心疾患 / 血管パッチ拡大 / 生体内組織工学 / 再生医療 / 同種移植 / 代用血管
Outline of Research at the Start

生体適合性を有し、抗血栓性に優れ、成長の可能性有する理想的な血管補填物の開発が望まれ、近年は組織工学的なアプローチが広く行われている。
我々は生体内組織工学技術により患者皮下で容易かつ安全に作製できる自己結合組織からなる代用血管の開発を行い、本技術を小児への肺動脈パッチ拡大術へ臨床応用し良好な経過を報告した。
本研究の目的は本技術の臨床応用をさらに推進させ、移植後長期に渡る安全性や成長可能性を確認することである。
一方で小児においては移植片を作製するために基材を埋入する皮膚の面積が限られてしまうことが危惧されるため、親の皮下で移植片を作製し子へ移植するという同種移植の応用を目指した基礎研究も行う。

Outline of Final Research Achievements

The development of ideal vascular grafts is critical. This study explores using tissue-engineered connective tissue membranes created subcutaneously as vascular grafts. We applied autologous connective tissue membranes from patients to the pulmonary artery patch enlargement procedure for congenital heart disease and confirmed their safety and good postoperative outcomes.
Given the limited skin area in pediatric patients, we also investigated allogeneic transplantation between parent and child through basic experiments. We created connective tissue membranes under the skin of Beagle dogs, decellularized them using surfactants, and transplanted them into the carotid arteries of other Beagle dogs. The patches maintained sufficient strength to withstand arterial pressure and did not develop aneurysms. Additionally, cell infiltration into the grafts was observed, suggesting the potential of these tissue-engineered membranes as vascular grafts.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した組織工学的手法で作製した結合組織膜は、理想的な血管補填物としての高い可能性を示した。
特に、先天性心疾患の小児患者に対する肺動脈パッチ拡大術への臨床応用において、全ての症例で術後の良好な経過と高い安全性が確認されたことは、学術的にも非常に重要である。
また、小児患者の皮膚面積の制約を考慮し、親子間の同種移植を視野に入れた基礎実験では、脱細胞処理後の移植片が動脈圧に耐える強度を保持し、移植後の細胞浸潤が確認されたことが大きな成果である。これらの結果は、本技術が将来的に移植・再生医療の進展に大きく寄与し、特に小児患者のQOLの向上に貢献する可能性を強く示している。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (32 results)

All 2024 2023 2022 2021 2020 2019

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results) Presentation (22 results) (of which Int'l Joint Research: 14 results)

  • [Journal Article] Genetically Modified Cell Transplantation Through Macroencapsulated Spheroids with Scaffolds to Treat Fabry Disease2021

    • Author(s)
      Kami Daisuke、Suzuki Yosuke、Yamanami Masashi、Tsukimura Takahiro、Togawa Tadayasu、Sakuraba Hitoshi、Gojo Satoshi
    • Journal Title

      Cell Transplantation

      Volume: 30 Pages: 096368972110602-096368972110602

    • DOI

      10.1177/09636897211060269

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A tissue-engineered, decellularized, connective tissue membrane for allogeneic arterial patch implantation2021

    • Author(s)
      Masashi Yamanami, Keiichi Kanda, Kazuki Morimoto, Tomoya Inoue, Taiji Watanabe, Osamu Sakai, Daisuke Kami, Satoshi Gojo, Hitoshi Yaku
    • Journal Title

      Artificial Organ

      Volume: Mar 12 2021 Issue: 4 Pages: 633-642

    • DOI

      10.1111/aor.14102

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modifications of the mechanical properties of in vivo tissue-engineered vascular grafts by chemical treatments for a short duration2021

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

      PLoS One

      Volume: Mar 12 2021 Issue: 3 Pages: e0248346-e0248346

    • DOI

      10.1371/journal.pone.0248346

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Short-Duration Ethanol Dehydration on Mechanical Properties of Porcine Pericardium2021

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

      Annals of Thoracic and Cardiovascular Surgery

      Volume: 27 Issue: 3 Pages: 169-175

    • DOI

      10.5761/atcs.oa.20-00133

    • NAID

      130008054430

    • ISSN
      1341-1098, 2186-1005
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell Transplantation Combined with Recombinant Collagen Peptides for the Treatment of Fabry Disease2020

    • Author(s)
      Kami D, Yamanami M, Tsukimura T, Maeda H, Togawa T, Sakuraba H, Gojo S.
    • Journal Title

      Cell Transplant

      Volume: 29 Pages: 963689720976362-963689720976362

    • DOI

      10.1177/0963689720976362

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histology and Mechanics of In Vivo Tissue-Engineered Vascular Graft for Children2020

    • Author(s)
      Fujita S, Yamagishi M, Kanda K, Maeda Y, Inoue T, Yamanami M, Watanabe T, Konishi E, Takeda-Miyata N, Yaku H
    • Journal Title

      Ann Thorac Surg

      Volume: Apr 28 2020 Issue: 3 Pages: 1050-1054

    • DOI

      10.1016/j.athoracsur.2020.03.069

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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
  • [Presentation] 同種由来結合組織膜を血管移植片として用いる試み:脱細胞処理の最適化と動物移植実験2024

    • Author(s)
      山南 将志、権代 竜郎、川尻 英長、小田 晋一郎、五條 理志、神田 圭一
    • Organizer
      第23回日本再生医療学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 振盪法による他家由来結合組織代用血管移植片の脱細胞化処理に関する基礎的検討2023

    • Author(s)
      権代 竜郎、山南 将志、神田 圭一、井上 知也、川尻 英長、渡辺 太治、上 大介、五條 理志、夜久 均
    • Organizer
      第51回日本血管外科学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] DEVELOPMENT OF A SIMPLE AND SHORT-TERM DECELLULARIZATION PROCEDURE FOR IN VIVO ALLOGENEIC TISSUE-ENGINEERED VASCULAR GRAFTS2023

    • Author(s)
      Gondai T, Yamanami M, Inoue T, Kawajiri H, Kami D, Gojo S, Oda S, Kanda K
    • Organizer
      the 49th European Society for Artificial Organs (ESAO) Congress
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体内組織工学技術を用いて患者皮下で作製する自家結合組織血管移植片の臨床応用拡大のための試み2022

    • Author(s)
      山南 将志,神田 圭一,権代 竜郎,川尻 英長,井上 知也,渡辺 太治,上 大介,五條 理志,前田 吉宣,小田 晋一郎,山岸 正明,夜久 均
    • Organizer
      第60回日本人工臓器学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 同種由来生体材料を血管移植片として用いるための脱細胞化処理方法最適化の試み2022

    • Author(s)
      権代 竜郎,山南 将志,神田 圭一,井上 知也,川尻 英長,渡辺 太治,上 大介,五條 理志,夜久 均
    • Organizer
      第60回日本人工臓器学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 先天性心疾患におけるIn Vivo Tissue-Engineered Vascular Graftの臨床応用2022

    • Author(s)
      小田 晋一郎,山岸 正明,山南 将志,前田 吉宣,浅田 聡,藤田 周平,本宮 久之,山下 英次郎,永瀬 崇,林 孝明,神田 圭一
    • Organizer
      第60回日本人工臓器学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] IMPROVEMENT OF THE SIMPLER AND SHORTER DECELLULARIZATION PROCEDURE OF IN VIMO TISSUE ENGINEERED VASCULAR GRAFT USED FOR ALLOGENEIC TRANSPLANTATION2022

    • Author(s)
      Gondai T, Yamanami M, Kanda K, Inoue T, Kawajiri H, Watanabe T, Kami D, Gojo S, Yaku H
    • Organizer
      the 48th European Society for Artificial Organs (ESAO) Congress
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Stenotic Pulmonary Artery Reconstruction Using in vivo Tissue Engineered Vascular Grafts2021

    • Author(s)
      Yoshinobu Maeda, Masaaki Yamagishi, Satoshi Asada, Hisayuki Hongu, Eijiro Yamashita, Hiroki Nakatsuji, Takashi Nagase, Rie Nakai, Keiichi Kanda, Tomoya Inoue, Masashi Yamanami, Hitoshi Yaku
    • Organizer
      American Heart Association Scientific Sessions 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 同種由来生体内組織工学血管移植片に対する脱細胞処理の最適化2021

    • Author(s)
      山南将志、神田圭一、井上知也、川尻英長、渡辺太治、上大介、五條理志、夜久均
    • Organizer
      第51回日本心臓血管外科学会学術総会
    • Related Report
      2020 Annual Research Report
  • [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

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Published: 2019-04-18   Modified: 2025-01-30  

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