Tissue Engineered Vessels and Valve constructed with Autologous Bone Marrow Cells Its Clinical Applications and Evaluations

• Project/Area Number: 17390387
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: YAMAMOTO Noboru (2007) Tokyo Women's Medical University, School of Medicine, Assistant professor (50297470); 新岡 俊治 (2005-2006) 東京女子医科大学, 医学研究科, 教授 (20192122)
• Co-Investigator(Kenkyū-buntansha): KUROSAWA Hiromi Tokyo Women's Medical University, School of Medicine, professor (50075511) ; MATSUMURA Goki Tokyo Women's Medical University, School of Medicine, Assistant professor (20297469) ; 石山 雅邦 東京女子医科大学, 医学部, 助手 (30246558) ; 山本 昇 東京女子医科大学, 医学部, 助手 (50297470) ; 小坂 由道 東京女子医科大学, 医学部, 助手 (90297507)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥15,150,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥1,350,000); Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2006: ¥4,500,000 (Direct Cost: ¥4,500,000); Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
• Keywords: Tissue Engineering / Vessels / Biodegradable Scaffold / Surgery / Clinical Application / Evaluation / Congenital Heart Disease / 生力学試験 / 生体吸収性ポリマー / 臨床応用 / フォンタン手術 / 中期遠隔成績 / 自己骨髄細胞 / 再生弁

Research Abstract

Prosthetic and bioprosthetic materials currently in use lack growth potential and therefore must be repeatedly replaced in pediatric cardiovascular patients as they grow. Tissue engineering is a new discipline that offers the potential for creating replacement structures from autologous cells and biodegradable scaffolds. In May 2000, we initiated clinical application of tissue-engineered vascular autografts (TEVAs) seeded with cultured cells. However, cell culturing is time-consuming, and xenoserum must be used. To overcome these disadvantages, we began to use bone marrow cells, readily available on the day of surgery, as a cell source.
Since September 2001, 44 patients had a cardiothoracic operation using TEVAs seeded with autologous bone marrow cells. Three to 10 mL/kg specimen of bone marrow was aspirated with the patient under general anesthesia before the skin incision. These cells were seeded onto the absorbable scaffold before implantation. This scaffold was composed of a copolym er of P (CL/LA) which degrades by hydrolysis. PLLA or PGA woven fabric were used for reinforcement of the scaffolds. Twenty-six tissue-engineered conduits and 19 tissue-engineered patches were used for the repair of congenital heart defects. Patients who had undergone this method had a catheterization study, CT scan, or both for the evaluation after the operation. Four late deaths due to the heart failure with or without multiple organ failure or brain bleeding in this series; these were unrelated to the TEVAs function. A few patient required PTA for the tubular graft-stenosis with pressure gradient and / or collaterals, and four patients for the stenosis of the tissue-engineered patch. However, this tissue-engineering approach may provide an important alternative to the use of prosthetic materials in the field of pediatric cardiovascular surgery. As it utilizes living autologous living tissue, this newly developed vascular structure may have the potential to achieve "auto-tissue repair" for the children with congenital heart defects. However, this approach is still in its infancy, further experimental studies to resolve the problems presented, and longer follow-up in patients are necessary to confirm the durability of this approach.

Research Products

• [Journal Article] 自己骨髄細胞と生体吸収性ポリマーにより作製した再生血管による臨床研究44症例とその経過 (2007)
  • Author(s): 松村 剛毅、新岡 俊治、日比野 成俊、斎藤 聡, 坂本 貴彦、市原 有起、保々 恭子、宮本 真嘉、黒澤 博身
  • Journal Title: 日心外会誌 36,6 Pages: 309-314
  • NAID: 110006453948
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Shin' ka Miyamoto, and Hiromi Kurosawa, Mid-term Clinical Results of Tissue-Engineered Vascular Autografts (2007)
  • Author(s): Goki, Matsumura, Toshiharu, Shin' oka, Narutoshi, Hibino, Satoshi, Saito, Takahiko, Sakamoto, Yuki, Ichihara, Kyoko, Hobo
  • Journal Title: The Japanese Society for Cardio- vascular Surgery 36(6) Pages: 309-314
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 自己骨髄細胞と生体吸収性ポリマーにより作製した再生血管による臨床研究44症例とその経過. (2007)
  • Author(s): 松村剛毅、新岡俊治、日比野成俊、斎藤聡、坂本貴彦、市原有起、保々恭子、宮本真嘉、黒澤博身
  • Journal Title: 日心外会誌 36,6 Pages: 309-314
  • NAID: 110006453948
  • Peer Reviewed
• [Journal Article] Hemodilutional anemia impairs neurologic outcome after cardiopulmonary bypass in a piglet model (2007)
  • Author(s): Miura T
  • Journal Title: J Thorac Cardiovasc Surg 133(1) Pages: 29-29
• [Journal Article] Evaluation of Tissue-Engineered Vascular Autografts (2006)
  • Author(s): Goki Matsumura, Yoko Ishihara, Sachiko-Miyagawa Tomita, Yoshito Ikada, Shojiro Matsuda, Hiromi Kurosawa, Toshiharu Shin'oka
  • Journal Title: Tissue Engineering 12 Pages: 3075-3083
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Evaluation of Tissue Engineered Vascular Autografts (2006)
  • Author(s): Goki, Matsumura, Yoko, Ishihara, Sachiko, M., Tomita, Yoshito, Ikada, Shojiro, Matsuda, Hiromi, Kurosawa, Toshiharu, Shin' oka
  • Journal Title: Tissue Engineering 12(11) Pages: 3075-3083
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Evaluation of Tissue-Engineered Vascular Autografts (2006)
  • Author(s): Matsumura G
  • Journal Title: Tissue Engineering 12(11) Pages: 3075-3075
• [Journal Article] 先天性心疾患領域における再生医療・Tissue Engineeringの展望 (2006)
  • Author(s): 市原 有起
  • Journal Title: 小児外科 38(2) Pages: 239-239
• [Journal Article] 組織工学による心臓弁、血管再生 (2006)
  • Author(s): 宮本 真嘉
  • Journal Title: 医学のあゆみ 217(5) Pages: 424-424
• [Journal Article] 培養人工血管-TissueEngineering Graft- (2006)
  • Author(s): 保々 恭子
  • Journal Title: 分子心血管病 7(5) Pages: 503-503
• [Journal Article] Midterm clinical result of tissue-engineered vascular autografts seeded pith autologous bone marrow cells (2005)
  • Author(s): Shin'oka, T.、Matsumura, G.、Hibina, N.、Naito, Y.、Watanabe, M.、Ronuma, T.、Sakamoto, T.、Nagatsu, M.、Kurosawa, H.
  • Journal Title: Journal of Thoracic and Cardiovascular Surgery 129,6 Pages: 1330-1338
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The tissue-engineered vascular graft using bone marrow without culture (2005)
  • Author(s): Hibino, N., Shin'oka, T., Matsumura, G., Ikada, Y., Kurosawa, H.
  • Journal Title: Journal of Thoracic and Cardiovascular Surgery 129,5 Pages: 1064-1070
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Midterm clinical result of tissue-engineered vascular autografts seeded with autologous bone marrow cells (2005)
  • Author(s): Shin'oka, T., Matsumura, G., Hibino, N., Naito, Y., Watanabe, M., Konuma, T., Sakamoto, T., Nagatsu, M., Kurosawa, H
  • Journal Title: J Thorac Cardiovasc Surg 129, 6 Pages: 1330-1330
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The tissue-engineered vascular graft using bone marrow without culture (2005)
  • Author(s): Hibino, N.,Shin'oka, T.,Matsumura, G., Ikada, Y., Kurosawa, H
  • Journal Title: J Thorac Cardiovasc Surg 129, 5 Pages: 1064-1064
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical Appl-ication of Tissue-Engineered Blood Vessels Engineering (2005)
  • Author(s): Goki, Matsumura, Toshiharu, Shin'oka
  • Journal Title: Cardiovascular Regeneration Therapies Using Tissue Approaches,Springer-Verlag Tokyo 105
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The tissue-engineered vascular graft using bone marrow without culture (2005)
  • Author(s): Hibino N, Shin'oka T, Matsumura G, Ikada Y, Kurosawa H
  • Journal Title: J Thorac Cardiovasc Surg 129 Pages: 1064-1070
• [Journal Article] Autopericardial patch tracheoplasty for tracheal stenosis after arterial switch operation (2005)
  • Author(s): Takiguchi M, Aoki M, Shin'oka T, Hiramatsu T, Imai Y
  • Journal Title: J Card Surg 20 Pages: 244-246
• [Journal Article] A successful total cavopulmonary connection conversion 13 years after an anatomic repair for tricuspid atresia IIc with severe pulmonary resistance (2005)
  • Author(s): Sugimoto K, Kurosawa H, Shin'oka T, Nagatsu M, Morishima S
  • Journal Title: J Thorac Cardiovasc Surg 129 Pages: 684-685
• [Journal Article] One-stage intracardiac repair in combination with external stenting of the trachea and right bronchus for tetralogy of Fallot (2005)
  • Author(s): Sakamoto T, Nagase Y, Hasegawa H, Shin'oka T, Tomimatsu H, Kurosawa
  • Journal Title: J Thorac Cardiovasc Surg 130 Pages: 1717-1718
• [Journal Article] Successful Application of Pulmonary Arterial Patch for Coronary Angioplasty Late after Arterial Switch Operation (2005)
  • Author(s): Kosaka Y, Shin'oka T, Yamazaki K, Kurosawa H
  • Journal Title: Jpn J Thorac Cardiovasc Surg 53 Pages: 601-603
  • NAID: 10016903731
• [Journal Article] Mid-term clinical results of tissue engineered vascular autografts seeded with autologous bome marrow cells (2005)
  • Author(s): Shin'oka T, Matsumura G, Hibino N, Naito Y, Watanabe M, Konuma T, Sakamoto T, Nagatsu M, Kurosawa
  • Journal Title: J Thorac Cardiovasc Surg 129 Pages: 1330-1338
• [Presentation] A Novel Therapy Using Tissue Engineering Vascular Autografts (2007)
  • Author(s): Goki Matsumura, Toshiharu Shin' oka, Kazuaki Ishihara, Takahiko Sakamoto, Yusuke Iwata, Noboru Yamamoto, Narutoshi Hibino, Yuki Ichihara, Shin' ka Miyamoto, Kyoko Hobo, Hiromi Kurosawa and Hiromi Kurosawa
  • Organizer: Japanese Society of Pediatric Cardiology and Cardiac Surgery
  • Place of Presentation: Tokyo
  • Year and Date: 2007-07-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 単心室症に対する心室中隔形成術の検討 (2007)
  • Author(s): 山本 昇、黒澤 博身、石原 和明、坂本 貴彦、岩田 祐輔、松村 剛毅、日比野 成俊、山崎 暁、小林 豊
  • Organizer: 第43回日本小児循環器学会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2007-07-04
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Arterial switch operation(ASO)術後遠隔成績と社会的自立度の検討 (2007)
  • Author(s): 山本 昇、黒澤 博身、新岡 俊治、石山 雅邦、坂本 貴彦、森嶋 克昌、松村 剛毅、日比野 成俊、石橋 信之、矢野 清崇
  • Organizer: 第37回日本心臓血管外科学会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2007-02-21
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Mid-term Clinical Results of Tissue-Engineered Vascular Autografts (2007)
  • Author(s): Goki Matsumura, Toshiharu Shin' oka, Narutoshi Hibino, Satoshi Saito, Takahiko Sakamoto, Yuki Ichihara, Kyoko Hobo, Shin' ka Miyamoto, and Hiromi Kurosawa
  • Organizer: The Japanese Society for Cardio- vascular Surgery
  • Place of Presentation: Tokyo
  • Year and Date: 2007-02-21
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Time Coarse Evaluations of Tissue Engineered Grafts (2000)
  • Author(s): Goki Matsumura, Toshiharu Shin' oka, Satoshi Saito, Takahiko Sakamoto, Yoshimichi Kosaka, Yuki Ichihara, Shin' ka Miyamoto, Kyoko Hobo, Hiromi Kurosawa
  • Organizer: The Japanese Society for Cardio-vascular Surgery
  • Place of Presentation: Morioka
  • Year and Date: 2000-04-14
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Clinical Application of Tissue-Engineered Blood Vessels:Cardiovaseular Regeneration Therapies Using Tissue Engineering Approaches (2005)
  • Author(s): Goki Matsumura, Toshiharu Shin'oka
  • Total Pages: 105
  • Publisher: Springer-Verlag Tokyo
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Cardiovascular Regeneration Therapies Using Tissue Engineering Approaches (2005)
  • Author(s): Matsumura G, Shin'oka T
  • Total Pages: 238
  • Publisher: Springer