Development of new endovascular therapy for aortic dicease with cell transplantation and drug delivery system, for applying to clinical use

• Project/Area Number: 17390378
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Mie University
• Principal Investigator: SHIMONO Takatsugu Mie University, Graduate School of Medicine, Associate Professor (80206242)
• Co-Investigator(Kenkyū-buntansha): KATO Noriyuki Mie University, Graduate School of Medicine, Associate Professor (40214390) ; MIYAMOTO Keigi Mie University, Graduate School of Engineering, Associate Professor (70252343) ; HIRATA Hitoshi Nagoya University, Graduate School of Medicine, Professor (80173243)
• Project Period (FY): 2005 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥16,670,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥870,000); Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2005: ¥10,000,000 (Direct Cost: ¥10,000,000)
• Keywords: Aortic aneurysm / Endovascular surgery / Stent-Graft / Cell transplantation / Fibroblast / Myoblast / Drug Delivery System

Research Abstract

We demonstrated previously that transplantation of a cell combination(myoblasts and fibroblasts) promoted thrombus organization in a rat model. We also developed basic fibroblast growth factor(bFGF) slow-delivery stent grafts(S/Gs) coated with elastin and impregnated with bFGF. In this project, the effects of cell transplantation combined with bFGF slow release on canine thoracic aortic aneurysmal sacs after S/Gs repair were evaluated.
Thoracic aortic aneurysms were surgically created with jugular vein patches in 15 beagles. Myoblasts and fibroblasts of autologous skeletal muscle were isolated for cell transplantation. The S/Gs with 6 holes were used in this experiment as endoleaking models. Collagen gel alone(control group n=5) or a mixture of skeletal and fibroblasts with collagen gel(cell group n=5) were injected into the aneurysmal sac excluded S/Gs. The combined therapy of bFGF slow-release S/Gs and cell therapy(hybrid group n=5) was also evaluated. After 14 days, histological analyses revealed that the excluded aneurysmal cavities of the control group were filled with fresh thrombus, whereas the excluded cavities in the cell group and the hybrid group were occupied by organized tissue. The percentages of the organized areas relative to the excluded cavities, evaluated by Masson's trichrome staining, were 18.1%, 52.6% and 77.1% in the control, cell, and hybrid groups, respectively. Also we evaluated some bio-gels for the injection into the anurysmal cavities with autolougus cells and concluded that autologus fibrin glue was suitable for this purpose.
Cell transplantations into excluded aneurysmal cavity with bFGF slow-release stent grafts may improve results of endovascular surgery for aortic aneurysms, especially against the type II endoleak

Research Products

• [Journal Article] Thoracic CT Findings Following Endovascular Stent-Garaft Treatment for Thoracic Aortic Aneurysm (2007)
  • Author(s): Ishida M, Kato N, Hirano T, Shimono T, Shimpo H, Takeda K.
  • Journal Title: Journal of Endovasc. Ther. 14 Pages: 333-341
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Thoracic CT Findings Following Endovascular Stent-Garaft Treatment for Thoracic Aortic Aneurysm (2007)
  • Author(s): Ishida, M, Kato, N, Hirano, T, Shimono, T, Shimpo, H, Takeda, K
  • Journal Title: Journal of Endovasc. Ther 14 Pages: 333-341
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Thoracic CT Findings Following Endovascular Stent-Garaft Treatmentfor Thoracic Aortic Aneurysm (2007)
  • Author(s): Ishida M, Kato N, Hirano T, Shimono T, Shimpo H, Takeda K.
  • Journal Title: Journal of Endovasc.Ther. 14 Pages: 333-341
  • Peer Reviewed
• [Journal Article] Development of a new method for endovascular aortic repair: combination therapy of cell transplantation and stent grafts with a drug delivery system. (2006)
  • Author(s): Kajimoto M, Shimno T, Hirano k, Miyake Y, Sawada Y, Kato N, Hirata H, Imanaka-Yoshida K, Nishikawa M, Yoshida T, Shimpo H, Horiuchi T, Miyamoto K.
  • Journal Title: Circulation 114 Pages: 1378-83
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Development of a new method for endovascular aortic repair : combination therapy of cell transplantation and stent grafts with a drug delivery system (2006)
  • Author(s): Kajimoto, M, Shimono, T, Hirano, K, Miyake, Y, Sawada, Y, Kato, N, Hirata, H, Imanaka-, Yoshida, K, Nishikawa, M, Yoshida, T, Shimpo, H, Horiuchi, T, Miyamoto, K
  • Journal Title: Circulation 114 Pages: 1378-83
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Development of a New Method for Endovascular Aortic Repair Combination Therapy of Cell Transplantation and Stent Grafts With a Drug Delivery System (2006)
  • Author(s): M Kajimonoto, T Shimoo, K Hirano, Y Miyake, Y Sawada, N Kato, H Hirata, K Imanaka-Yoshida, M Nishikawa, T Yoshida, H Shimpo, T Horiuchi, K Miyamoto
  • Journal Title: Circulation 114 (suppll)
• [Journal Article] Method of cell transplantation promoting the organization of intraarterial thrombus. (2005)
  • Author(s): Hirano k, Shimno T, Imanaka-Yoshida K, Miyamoto K, Fujinaga K, Kajimoto M, Miyake Y, Nishikawa M, Yoshida T, Uchida A, Shimpo H, Yada I, Hirata H.
  • Journal Title: Circulation 112
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Changes in false lumen after transluminal stent-graft placement in aortic dissections: six year's expenence. (2005)
  • Author(s): Kusagawa H, Shimono T, Ishida M, Suzauki T, Yasuda F, Yuasa U, Onoda K, Yada I, Hirano T, Takeda K, Kato N.
  • Journal Title: Circulation 111 Pages: 2951-7
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Contrast-enhanced MR imaging for evaluation of coronary artery disease before elective repair of aortic aneurysm. (2005)
  • Author(s): Ishida M, Sakuma H, Kato N, Ishida N, Kitagawa K, Shimono T, Yada I, Takeda K.
  • Journal Title: Radiology 237 Pages: 458-64
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Method of cell transplantation promoting the organization of intraarterial thrombus (2005)
  • Author(s): Hirano, K, Shimono, T, Imanaka-Yoshida, K, Miyamoto, K, Fujinaga, K, Kajimoto, M, Miyake, Y, Nishikawa, M, Yoshida, T, Uchida, A, Shimpo, H, Yada, I, Hirata, H
  • Journal Title: Circulation 112 Pages: 1111-6
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Changes in false lumen after transluminal stent-graft placement in aortic dissections : six years' experience (2005)
  • Author(s): Kusagawa, H, Shimono, T, Ishida, M, Suzuki, T, Yasuda, F, Yuasa, U, Onoda, K, Yada, I, Hirano, T, Takeda, K, Kato, N
  • Journal Title: Circulation 111 Pages: 2951-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contrast-enhanced MR imaging for evaluation of coronary artery disease before electiverepair of aortic aneurysm (2005)
  • Author(s): Ishida, M, Sakuma, H, Kato, N, Ishida, N, Kitagawa, K, Shimono, T, Yada, I, Takeda, K
  • Journal Title: Radiology 237 Pages: 458-64
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Method of cell transplantation promoting the organization of intraarterial thrombus. (2005)
  • Author(s): Hirano K, Shimono T, Imanaka-Yoshida K, Miyamoto K, Fujinaga K, Kajimoto M, Miyake Y, Nishikawa M, Yoshida T, Uchida A, Shimpo H, Yada I, Hirata H.
  • Journal Title: Circulation 112(9 Suppl) Pages: 111-116
• [Presentation] Enodvascular stent grafting for perforated acute aortic dissections, ruptured aorticaneurysms and traumatic aortic rupture (2007)
  • Author(s): Hirano K, Shimono T, Ozu Y, Yokoyama K, Sawada Y, et. al.
  • Organizer: The 15th Annual Meeting of Asian Society for Cardio-Vascular Surgery
  • Place of Presentation: 北京市 中華人民共和国
  • Year and Date: 2007-05-17
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Enodvascular stent grafting for perforated acute aortic dissections, ruptured aorticaneurysms and traumatic aortic rupture (2007)
  • Author(s): Hirano, K, Shimono, T, Ozu, Y, et. al
  • Organizer: The 15th. Annual Meeting of Asian Society for Cardio-Vascular Surgery
  • Place of Presentation: Beijing China
  • Year and Date: 2007-05-17
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Enodvascular stent grafting for perforated acute aortic dissections, ruptured aortic aneurysms and traumatic aortic rupture (2007)
  • Author(s): Hirano K, Shhnono T, Ozu Y, Yokoyama K, Sawada Y, et.al.
  • Organizer: The 15th Annual Meeting of Asian Society for Cardio-Vascular Surgery
  • Place of Presentation: 北京市 中華人民共和国
  • Year and Date: 2007-05-17
• [Presentation] Regenerative Cell Therapy for Endovascular Aortic Repair (2007)
  • Author(s): Shimono T.
  • Organizer: Scientific Clinical Workshop Tissue Regeneration
  • Place of Presentation: ロストック市 ドイツ
  • Year and Date: 2007-03-31
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Regenerative Cell Therapy for Endovascular Aortic Repair (2007)
  • Author(s): Shimono, T
  • Organizer: Scientific Clinical Workshop Tissue Regeneration 2007
  • Place of Presentation: Rostock, Germany
  • Year and Date: 2007-03-31
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 大動脈瘤に対する血管内治療における再生医療の応用を目指して (2006)
  • Author(s): 下野高嗣、梶本政樹、平野弘嗣、新保秀人、宮本啓一、石田正樹、ほか
  • Organizer: 第44回日本人工臓器学会
  • Place of Presentation: 東京都
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Development of a New Method for Endovascular Aortic Repair, Combination Therapy of Cell Transplantation and Stent-Graft with a Drug Delivery System (2005)
  • Author(s): Kajimoto M, Shimono T, Hirano H, Miyake Y, Sawada Y, et. al.
  • Organizer: AHA Scientific Sessions 2005
  • Place of Presentation: ダラス 米国
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 大動脈瘤に対する新しい血管内治療法の開発-薬剤徐放能付加Stent-Graftと自己細胞移植療法- (2005)
  • Author(s): 梶本政樹、下野高嗣、平野弘嗣、三宅陽一郎、澤田康裕、宮本啓一、ほか
  • Organizer: 第105回日本外科学会定期学術集会
  • Place of Presentation: 名古屋市
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Development of a New Method for Endovascular Aortic Repair, Combination Therapy of Cell Transplantation and Stent-Graft with a Drug Delivery System (2005)
  • Author(s): Kajimoto, M, Shimono, T, Hirano, K, et. al
  • Organizer: AHA Scientific Sessions 2005
  • Place of Presentation: Dallas Tx. U.S.A.
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Annual Review循環器 IV. 心臓血管外科 6.ステントグラフトによるB型大動脈解離の治療 (2007)
  • Author(s): 下野高嗣 編集:山口 徹、高本眞一、中沢 誠、小室一成
  • Publisher: 中外医学社
  • Description: 「研究成果報告書概要(和文)」より