Hybrid therapy for chronic critical limb ischemia-combination of gene transfer via Sendai virus and endothelial cell plantation.

• Project/Area Number: 20591520
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Nagoya University
• Principal Investigator: KOBAYASHI Masayoshi Nagoya University, 医学部附属病院, 助教 (60329381)
• Co-Investigator(Kenkyū-buntansha): KOMORI Kimihiro 名古屋大学, 大学院・医学系研究科, 教授 (40225587) ; YAMAMOTO Kiyohito 名古屋大学, 医学部附属病院, 講師 (10298359)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 重症虚血肢 / 遺伝子治療 / ハイブリッド治療 / シロスタゾール / メトフェルミン

Research Abstract

Our final goal is that hybrid therapy combined gene transfer via Sendai virus with bone marrow or peripheral blood cell transplantation can be completed. In this preliminary study, we investigated whether cilostazol induces improvement of blood flow in the ischemic hindlimb of mouse, and if so, examined the mechanisms of angiogenesis. Based on our results, cilostazol caused angiogenesis in ischemic hindlimb model of mouse. This angiogenesis may be due to the enhancement of nitric oxide production. Our final destination is that hybrid therapy with a combination between gene transfer via Sedai virus and cell transplantation can be established in near future.

Research Products

• [Journal Article] Immunohistochemical properties in the patients with Buerger's disease-Possible role of Plasminogen Activator Inhibitor-1(PAI-1) for preservation of vessel wall architecture (2010)
  • Author(s): Sato T, Kobayashi M, Yamamoto K, Komori K
  • Journal Title: Cardiovascular Pathology in press
  • Peer Reviewed
• [Journal Article] Evaluation of the Efficacy of Venous Thromboembolism Prophylaxis Guideline Implementation in Japan (2010)
  • Author(s): Niimi K, Kobayashi M, Narita H, Yamamoto K, Komori K
  • Journal Title: Surg Today 40 Pages: 1129-1136
  • NAID: 10027657356
  • Peer Reviewed
• [Journal Article] 血管外科領域におけるトランスレーショナルリサーチ-Nitric Oxideとセロトニン- (2010)
  • Author(s): 古森公浩
  • Journal Title: 第38回日本血管外科学会学術総会ランチョンセミナー記録集 Angiology Frontier Vo1.9 No.3
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic Acid as the Gold Standard for Patients With Peripheral Artery Disease?-Subanalysis of the JELIS Trial- (2010)
  • Author(s): Yamanouchi D, Komori K
  • Journal Title: Circulation Journal Vol.74 No.7 Pages: 298-1299
  • NAID: 10030695193
  • Peer Reviewed
• [Journal Article] 重症下肢虚血に対する外科的治療戦略新・心臓病診療プラクティス (2010)
  • Author(s): 森前博文, 古森公浩
  • Journal Title: 血管疾患を診る・治す 15 Pages: 232-234
  • Peer Reviewed
• [Journal Article] Immunohistochemical properties in the patients with Buerger's disease-Possible role of Plasminogen Activator Inhibitor-1(PAI-1) for preservation of vessel wall architecture (2010)
  • Author(s): Sato T, Kobayashi M, YamamotoK, Komori K
  • Journal Title: Cardiovascular Pathology Volume: in press
  • Peer Reviewed
• [Journal Article] Evaluation of the Efficacy of Venous Thromboembolism Prophylaxis Guideline Implementation in Japan (2010)
  • Author(s): Niimi K, Kobayashi M, Narita H, Yamamoto K, Komori K
  • Journal Title: Surg Today Volume: 40 Pages: 1129-1136
  • NAID: 10027657356
  • Peer Reviewed
• [Journal Article] 血管外科領域におけるトランスレーショナルリサーチ-Nitric Oxideとセロトニン-第38回日本血管外科学会学術総会ランチョンセミナー記録集 (2010)
  • Author(s): 古森公浩
  • Journal Title: Angiology Frontier Volume: 9 Pages: 90-95
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic Acid as the Gold Standard for Patients With Peripheral Artery Disease?-Subanalysis of the JELIS Trial- (2010)
  • Author(s): Yamanouchi D, Komori K
  • Journal Title: Circulation Journal Volume: 74 Pages: 1298-1299
  • NAID: 10030695193
  • Peer Reviewed
• [Journal Article] 動脈硬化に対する細胞移植療法 Therapeutic angiogcnesis for the patients with peripheral arterial disease (2009)
  • Author(s): 小林昌義, 古森公浩
  • Journal Title: 総合臨床 VOL.58 no.a Pages: 1817-1819
  • Peer Reviewed
• [Journal Article] Chronic treatment of hydroxytryptamine type 2a receptor antagonist sarpogrelate hydrochloride modulates the vasoreactivity of scrotonin in experimental rabbit vein grafts (2009)
  • Author(s): Kodama A, Komori K, Kajikuri J, Itch T
  • Journal Title: J Vase Surg 50 Pages: 617-625
  • Peer Reviewed
• [Journal Article] Sarpogrelate hydrochloride reduced intimal hyperplasia in experimental rabbit vein graft (2009)
  • Author(s): Kodama A, Komori K, Hattori K, Yamanouchi D, Kajikuri J, Itch T
  • Journal Title: J Vase Surg 49z(5) Pages: 1272-1281
  • Peer Reviewed
• [Journal Article] Therapeutic Approach Against Intimal Hyperplasia of Vein Grafts Through Endothelial Nitric Oxide Synthase/Nitric Oxide(eNOS/NO)and the Rho/Rho-Kinase Pathway (2009)
  • Author(s): Sugimoto M, Yamanouchi D, Komori K
  • Journal Title: Surgery Today 39 Pages: 459-465
  • NAID: 10025132704
  • Peer Reviewed
• [Journal Article] Sarpogrelate hydrochloride reduced intimal hyperplasia in experimental rabbit vein graft (2009)
  • Author(s): Kodama A, Komori K, Hattori K, Yamanouchi D, Kajikuri J, Itoh T
  • Journal Title: JOURNAL OF VASCULAR SURGERY 49 Pages: 1272-1281
  • Peer Reviewed
• [Journal Article] 動脈硬化に対する細胞移植療法 (2009)
  • Author(s): 小林昌義、古森公浩
  • Journal Title: 総合臨床 58 Pages: 1817-1819
• [Journal Article] (2009)
  • Author(s): 古森公浩
  • Journal Title: 標準血管外科学II(メディカルトリビューン) Pages: 88-94
• [Journal Article] (2009)
  • Author(s): 古森公浩
  • Journal Title: 標準血管外科学II(メディカルトリビューン) Pages: 123-126
• [Journal Article] 特集重症虚血肢に対する診療指針重症虚血肢の疫学,合併疾患,生命予防について (2008)
  • Author(s): 杉本昌之, 古森公浩
  • Journal Title: AngiologyFrontier Vol.7 No.2 Pages: 11-15
  • Peer Reviewed
• [Journal Article] 序文とまとめ-心血管病に対する再生医療- (2008)
  • Author(s): 古森公浩
  • Journal Title: 脈管学 47 Pages: 475-475
  • NAID: 10021261529
  • Peer Reviewed
• [Journal Article] Serum procalcitonin(PCT) is a reliable marker for ischemic complication of intestine after open abdominal aortic surgery (2008)
  • Author(s): 永田純一
  • Journal Title: European Journal of Vascular and Endvascular Surgery 35 Pages: 694-697
  • Peer Reviewed
• [Journal Article] Pitavastatin Inhibits Intimal Hyperplasia in Rabbit Vein Graft (2008)
  • Author(s): 藤田広峰
  • Journal Title: Journal of Surgical Research 148 Pages: 238-243
  • Peer Reviewed
• [Journal Article] Midkine is expressed by infiltrating macrophages in in-stent Restenosis in hypercholesteremic rabbits (2008)
  • Author(s): 成田裕司
  • Journal Title: Journal of Vascular Surgery 47 Pages: 1322-9
  • Peer Reviewed
• [Presentation] Cilostazol Causes Angiogenesis Mediated Through the Enhancement of Nitric Oxide Production in the ischemic Hindlimb of Mouse (2010)
  • Author(s): Hori A, Shibata R, Kobayashi M, Yamamoto K, Komori K
  • Organizer: The 11th Annual Congress of Asian Society for V ascular Surgery
  • Place of Presentation: The Westin Miyako, Kyoto, Japan
  • Year and Date: 2010-07-01
• [Presentation] Cilostazol Causes Angiogenesis Mediated through the Enhancement of Nitric Oxide Production in the Ischemic Hindlimb of Mouse (2010)
  • Author(s): Hori K, Shibata R, Narita H, Kobayashi M, Yamamoto K, Komori K
  • Organizer: 2010 Vascular Annual Meeting
  • Place of Presentation: Hynes Convention Center, Boston, Massachusetts, USA
  • Year and Date: 2010-06-11
• [Presentation] 血行障害による下肢潰瘍/壊疽に対する治療戦略とその成績 (2010)
  • Author(s): 小林昌義, 森崎浩一, 前川卓史, 玉井宏明, 高橋範子, 森前博文, 井原努, 堀昭彦, 成田裕司, 山本清人, 古森公浩
  • Organizer: 第38回日本血管外科学会総会
  • Place of Presentation: 大宮ソニックシティ・パレスホテル大宮
  • Year and Date: 2010-05-21
• [Presentation] 血行障害による下肢潰瘍/壊疽に対する治療戦略とその成績 (2010)
  • Author(s): 小林昌義, 森崎浩一, 前川卓史, 玉井宏明, 高橋範子, 森前博文, 井原努, 堀昭彦, 成田裕司, 山本清人, 古森公浩
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2010-04-10
• [Presentation] 末梢動脈疾患の最新の治療戦略-新しい治療ガイドラインを踏まえて- (2010)
  • Author(s): 古森公浩
  • Organizer: 第15回関東甲信越セロトニン研究会
  • Place of Presentation: 経団連会館
  • Year and Date: 2010-01-30
• [Presentation] Cilostazol Causes Angiogenesis Mediated Through the Enhancement of Nitric Oxide Production in the ischemic Hindlimb of Mouse (2010)
  • Author(s): Hori A, Shibata R, Kobayashi M, Yamamoto K, Komori K
  • Organizer: The 11th Annual Congress of Asian Society for Vascular Surgery
  • Place of Presentation: The Westin Miyako, Kyoto, Japan
• [Presentation] Current Status of Therapeutic Angiogenesis for the Patients with Peripheral Arterial Disease in Japan (2010)
  • Author(s): 古森公浩
  • Organizer: The 11th Annual Congress of Asian Society for Vascular Surgery
  • Place of Presentation: The Westin Miyako, Kyoto, Japan
• [Presentation] Differences in the Endothelial Function and Morphological Modulation between the Canine Autogenous Vein and Arterial Grafts Endothelium and Intimal Thickening (2010)
  • Author(s): 古森公浩
  • Organizer: The 6th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Japan
• [Presentation] Cilostazol Causes Angiogencsis Mediated through the Enhancement of Nitric Oxide Production in the Ischemic Hindlimb of Mouse (2010)
  • Author(s): Hori K, Shibata R, Narita H, Kobayashi M, Yamamoto K, Komori K
  • Organizer: 2010 Vascular Annual Meeting
  • Place of Presentation: Hynes Convention Center, Boston, Massachusetts, USA
• [Presentation] 血行障害による下肢潰瘍/壊疽に対する治療戦略とその成績 (2010)
  • Author(s): 小林昌義, 森崎浩一, 前川卓史, 玉井宏明, 高橋範子, 森前博文, 井原努, 堀昭彦, 成田裕司, 山本清人, 古森公浩
  • Organizer: 第38回日本血管外科学会総会
  • Place of Presentation: 大宮ソニソクシティ・パレスホテル大宮
• [Presentation] 当科における血管新生療法治療成績の検討と今後の展望 (2010)
  • Author(s): 堀昭彦, 森崎浩一, 前川卓史, 玉井宏明, 高橋範子, 森前博文, 井原努, 成田裕司, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第38回日本血管外科学会総会
  • Place of Presentation: 大宮ソニックシティ・パレスホテル大宮
• [Presentation] 血行障害による下肢潰瘍/壊疽に対する治療戦略とその成績 (2010)
  • Author(s): 小林昌義, 森崎浩一, 前川卓史, 玉井宏明, 高橋範子, 森前博文, 井原努, 堀昭彦, 成田裕司, 山本清人, 古森公浩
  • Organizer: 第11O回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] マウス虚血肢モデルに対するシロスタゾールの血管新生効果について (2010)
  • Author(s): 堀昭彦, 森崎浩一, 前川卓史, 玉井宏明, 高橋範子, 森前博文, 井原努, 成田裕司, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 血行障害による壊/潰瘍の治療経験について (2009)
  • Author(s): 小林昌義, 玉井宏明, 出津明仁, 森前博文, 児玉章朗, 堀昭彦, 成田裕司, 山本清人, 古森公浩
  • Organizer: 第1回東海創傷治療フォーラム
  • Place of Presentation: 科研製薬株式会社名古屋支店
  • Year and Date: 2009-01-30
• [Presentation] ウサギ自家静脈グラフトモデルにおけるセロトニンレセプターの検討-サルポグレラート塩酸塩投与の効果- (2009)
  • Author(s): 児玉章朗, 玉井宏明, 出津明仁, 森前博文, 堀昭彦, 成田裕司, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第16回東海セロトニン(5-HT_2)研究会
  • Place of Presentation: 名古屋クレストンホテル
  • Year and Date: 2009-01-24
• [Presentation] THERAPEUTIC ANGIOGENESIS FOR THE PATIENTS WITH PERIPHERAL ARTERIAL DISEASE (2009)
  • Author(s): 古森公浩
  • Organizer: The 10th Annual Congress of Asian Society for Vascular Surgery
  • Place of Presentation: BEXCO, Busan, Korea
• [Presentation] SARPOGRELATE HYDROCHLORIDE MODULATES THE EXPRESSION OF 5-HYDROXYTRYPTAMINE TYPE 2A AND TYPE 1B RECEPTORS IN EXPERIMENTAL RABBIT VEIN GRAFTS 10th MOVD 2009 (2009)
  • Author(s): Kodama A, Tamai H, Idetsu A, Morimae H, Hori A, Narita H, Kobayashi M, Yamamoto K, Kajikuri J, Itoh T, Komori K
  • Organizer: 10th International Symposium on Mechanisms of Vasodilatation
  • Place of Presentation: Hotel Taikanso Matsushima, Miyagi, Japan
• [Presentation] 下肢血行障害による下肢潰瘍/壊疽に対する治療法とその成績 (2009)
  • Author(s): 小林昌義, 玉井宏明, 出津明仁, 森前博文, 児玉章朗, 堀昭彦, 成田裕司, 山本清人, 古森公浩
  • Organizer: 第37回日本血管外科学会総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 当科における下肢虚血に対する無侵襲診断について (2009)
  • Author(s): 成田裕司, 古森公浩, 山本清人, 小林昌義, 堀昭彦, 児玉章朗, 森前博文, 出津明仁, 玉井宏明
  • Organizer: 第37回日本血管外科学会総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Sarpogrelate Hydrochloride Modulates the Expression of 5-Hydroxytryptamine Type 2A and Type 1B Receptors in Experimental Rabbit Vein Grafts (2009)
  • Author(s): Kodama A, Tamai H, Idetsu A, Morimae H, Hori A, Narita H, Kobayashi M, Yamamoto K, Komori K
  • Organizer: Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2009
  • Place of Presentation: Omni Shoreham Hotel, Washington, USA
• [Presentation] ウサギ自家静脈グラフトにおけるセロトニンレセプター発現の検討-塩酸サルポグレラート投与の効果- (2009)
  • Author(s): 児玉章朗, 玉井宏明, 出津明仁, 森前博文, 堀昭彦, 成田裕司, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 塩酸サルポグレラートによるウサギ自家静脈グラフト内膜肥厚抑制効果 (2009)
  • Author(s): 成田裕司, 玉井宏明, 出津明仁, 森前博文, 児玉章朗, 堀昭彦, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡国際会議場
• [Presentation] SARPOGRELATE HYDROCHLORIDE MODULATES THE EXPRESSION OF 5-HYDROXYTRYPTAMINE TYPE 2A AND TYPE 1B RECEPTORS IN EXPERIMENTAL RABBIT VEIN GRAFTS (2009)
  • Author(s): Kodama A
  • Organizer: 10th MOVD 2009, 10th International Symposium on Mechanisms of Vasodilatation
  • Place of Presentation: Matsushima, Miyagi, Japan
• [Presentation] Sarpogrelate Hydrochloride Reduced Intimal Hyperplasia in Experimental Rabbit Vein Graft -Possible Involvement of Enhancement of Nitric Oxide (NO) Production- (2008)
  • Author(s): 児玉章朗
  • Organizer: 2008 Vascular Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-06-04
• [Presentation] Clinical outcome of endovascular therapy for the patients with peripheral arterial disease. (2008)
  • Author(s): Yamamoto K, Morimae H, Narita H, Kobayashi M, Komori K
  • Organizer: The 5th Meeting of the Japanese-German Society for Vascular Surgery
  • Place of Presentation: Toba, Japan
• [Presentation] 下肢血行障害による下肢潰瘍/壊疽に対する治療法とその成績 (2008)
  • Author(s): 小林昌義, 玉井宏明, 出津明仁, 森前博文, 児玉章朗, 堀昭彦, 山本清人, 古森公浩
  • Organizer: 第14回血管内治療学会総会
  • Place of Presentation: アルカディア市ヶ谷
• [Presentation] Sarpogrelate Hydrochloride Reduced Intimal Hyperplasia in Experimental Rabbit Vein Graft-Possible Involvement of Enhancement of Nitric Oxide (NO) Production (2008)
  • Author(s): Kodama A, Idetsu A, Sugimoto M, Ihara T, Niimi K, Narita H, Kobayashi M, Yamamoto K, Itoh T, Komori K
  • Organizer: VASCULAR ANNUAL MEETING 2008
  • Place of Presentation: San Diego
• [Presentation] 当院での細胞移植療法の臨床成績と遺伝子治療とのハイブリッド治療効果 (2008)
  • Author(s): 井原努, 出津明仁, 杉本昌之, 新美清章, 児玉章朗, 成田裕司, 上遠野由紀, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎ブリックホール
• [Presentation] ステント再狭窄とMidkineとの関連について-高脂血症ウサギのステント再狭窄モデルでの検討- (2008)
  • Author(s): 成田裕司, 出津明仁, 杉本昌之, 井原努, 児玉章朗, 新美清章, 上遠野由紀, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎ブリックホール
• [Presentation] 重症虚血肢における血管内治療の役割 (2008)
  • Author(s): 山本清人, 出津明仁, 杉本昌之, 井原努, 新美清章, 児玉章朗, 成田裕司, 上遠野由紀, 小林昌義, 古森公浩
  • Organizer: 第36回日本血管外科学会学術総会
  • Place of Presentation: アルカディア市ヶ谷
• [Presentation] 閉塞性動脈硬化症患者の生命予後と予測関連因子 (2008)
  • Author(s): 新美清章, 出津明仁, 杉本昌之, 井原努, 児玉章朗, 成田裕司, 上遠野由紀, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第36回日本血管外科学会学術総会
  • Place of Presentation: アルカディア市ヶ谷
• [Presentation] 下肢末梢動脈瘤の検討 (2008)
  • Author(s): 成田裕司, 出津明仁, 杉本昌之, 井原努, 児玉章朗, 新美清章, 上遠野由紀, 小林昌義, 山本清人, 古森公浩
  • Organizer: 第36回日本血管外科学会学術総会
  • Place of Presentation: アルカディア市ヶ谷
• [Presentation] 閉塞性動脈硬化症の手術におけるpit fallと対策 (2008)
  • Author(s): 古森公浩
  • Organizer: 第36回日本血管外科学会学術総会
  • Place of Presentation: アルカディア市ヶ谷
• [Book] PADの分類(Fontaine分類とRutherford分類) (2010)
  • Author(s): 古森公浩
  • Publisher: 南山堂
• [Book] TASC IIの診断プロセス (2010)
  • Author(s): 古森公浩
  • Publisher: 南山堂
• [Book] PCI EVT (2010)
  • Author(s): 古森公浩
  • Publisher: 南山堂
• [Remarks] ホームページ等
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