Integrated cardiac stem cell therapy to treat heart failure

• Project/Area Number: 20390223
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Okayama University
• Principal Investigator: OH Hidemasa Okayama University, 病院, 教授 (50372579)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: 心臓内幹細胞 / 再生医療 / 細胞移植 / 心不全 / 成長因子 / 塩基性線維芽細胞成長因子 / 組織工学 / 心筋再生医療 / 細胞治療 / Sca-1 / bFGF / MURC / 増殖因子 / Akt / 突然変異 / 心筋構造蛋白 / 遺伝子欠損マウス

Research Abstract

Current cell therapies for cardiac repair are limited by loss of the transplanted cells and poor differentiation. Controlled delivery of bFGF modulates the post-ischemic microenvironment to enhance human cardiosphere-derived cell engraftment and differentiation. This novel strategy demonstrates significant functional improvements after myocardial infarction and may potentially represent a therapeutic approach to be studied in a clinical trial in human heart failure.

Research Products

• [Journal Article] PARM-1 is an Endoplasmic Reticulum Molecule Involved in Endoplasmic Reticulum Stress-induced Apoptosis in Rat Cardiac Myocytes. (2010)
  • Author(s): Isodono K, Takahashi T, Imoto H, Nakanishi N, Ogata T, Asada S, Adachi A, Ueyama T, Oh H, Matsubara H.
  • Journal Title: PLos ONE 18(5)
  • Peer Reviewed
• [Journal Article] 心臓再生医療 (2010)
  • Author(s): 内藤大督, 加藤拓, 片村真紀, 竹原有史, 王英正, 松原弘明
  • Journal Title: 循環器疾患のサイエンス Volume: 3 Pages: 231-235
• [Journal Article] PARM-1 is an Endoplasmic Reticulum Molecule Involved in Endoplasmic Reticulum Stress-induced Apoptosis in Rat Cardiac Myocytes. (2010)
  • Author(s): K.Isodono, T.Takahashi, H.Imoto, N.Nakanishi, T.Ogata, S.Asada, A.Adachi, T.Ueyama, H.Oh, H.Matsubara
  • Journal Title: PLoS ONE (印刷中)
  • Peer Reviewed
• [Journal Article] Stem cell engineering for cardiac tissue regeneration. (2010)
  • Author(s): Yoshida M, Oh H.
  • Journal Title: Cardiology 115 Pages: 191-193
  • Peer Reviewed
• [Journal Article] Deficiency of nectin-2 leads to cardiac fibrosis and dysfunction under chronic pressure overload. (2009)
  • Author(s): Satomi-Kobayashi S, Ueyama T, Mueller S, Toh R, Masano T, Sakoda T, Rikitake Y, Miyoshi J, Matsubara H, Oh H, Kawashima S, Hirata K, Takai Y.
  • Journal Title: Hypertension 54 Pages: 825-831
  • Peer Reviewed
• [Journal Article] Deficiency of nectin-2 leads to cardiac fibrosis and dysfunction under chronic pressure overload. (2009)
  • Author(s): Satomi Kobayashi S, Ueyama T, Mueller S, Toh R, Masano T, Sakoda T, Rikitake Y, Miyoshi J, Matsubara H, Oh H, Kawashima S, Hirata K, Takai Y.
  • Journal Title: Hypertension 54 Pages: 825-831
  • Peer Reviewed
• [Journal Article] 心筋幹細胞 (2009)
  • Author(s): 王英正
  • Journal Title: 循環器科 66 Pages: 453-460
• [Journal Article] 重症心不全に対する細胞治療法 (2009)
  • Author(s): 竹原有史、塘義明、天野克也、王英正、長谷部直幸、松原弘明
  • Journal Title: 循環器科 66 Pages: 392-399
• [Journal Article] 心筋幹細胞の臨床応用の可能性 : Cardiosphereによる心筋再生医療 (2009)
  • Author(s): 山口真一郎、竹原有史、天野克也、高橋知三郎、王英正、松原弘明
  • Journal Title: 分子心血管病 10 Pages: 40-47
• [Journal Article] Cardiosphereを用いた心筋再生医療 (2009)
  • Author(s): 中岡幹彦、竹原有史、中西直彦、赤壁佳樹、王英正、松原弘明
  • Journal Title: 再生医療 8 Pages: 74-81
• [Journal Article] Cardiosphere由来心臓幹細胞を用いた心筋再生医療 (2009)
  • Author(s): 中西直彦、竹原有史、中岡幹彦、赤壁佳樹、王英正、松原弘明
  • Journal Title: 綜合臨床 58 Pages: 591-598
• [Journal Article] Controlled Delivery of Basic Fibroblast Growth Factor Promotes Human Cardiosphere-Derived Cell Engraftment to Enhance Cardiac Repair for Chronic Myocardial Infarction. (2008)
  • Author(s): Takehara N, Tsutsumi Y, Tateishi K, Ogata T, Tanaka H, Ueyama T, Takahashi T, Takamatsu T, Fukushima M, Komeda M, Yamagishi M, Yaku H, Tabata Y, Matsubara H, Oh H.
  • Journal Title: Journal of American College of Cardiology 52 Pages: 1858-1865
  • Peer Reviewed
• [Journal Article] Stemming heart failure with cardiac- or reprogrammed-stem cells. (2008)
  • Author(s): Tateishi K, Takehara N, Matsubara H, Oh H.
  • Journal Title: Journal of Cellular and Molecular Medicine 12(6A) Pages: 2217-2232
  • Peer Reviewed
• [Journal Article] Crossveinless-2 controls bone morphogenetic protein signaling during early cardiomyocyte differentiation in p19 cells. (2008)
  • Author(s): Harada K, Ogai A, Takahashi T, Kitakaze M, Matsubara H, Oh H.
  • Journal Title: Journal of Biological Chemistry 283 Pages: 26705-26713
  • Peer Reviewed
• [Journal Article] Downregulation of Dicer expression by serum withdrawal sensitizes human endothelial cells to apoptosis. (2008)
  • Author(s): Asada S, Takahashi T, Isodono K, Adachi A, Imoto H, Ogata T, Ueyama T, Matsubara H, Oh H.
  • Journal Title: American Journal of Physiology Cell Physiology 295
  • Peer Reviewed
• [Journal Article] MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis. (2008)
  • Author(s): Tagawa M, Ueyama T, Ogata T, Takehara N, Nakajima N, Isodono K, Asada S, Takahashi T, Matsubara H, Oh H.
  • Journal Title: American Journal of Physiology Cell Physiology 295
  • Peer Reviewed
• [Journal Article] MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance. (2008)
  • Author(s): Ogata T, Ueyama T, Isodono K, Tagawa M, Takehara N, Kawashima T, Harada K, Takahashi T, Shioi T, Matsubara H, Oh H.
  • Journal Title: Molecular and Cellular Biology 28 Pages: 3424-3436
  • Peer Reviewed
• [Journal Article] MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance (2008)
  • Author(s): Ogata T, Ueyama T, Isodono K, Tagawa M, Takehara N, Kawashima T, Harada K, Takahashi T, Shioi T, Matsubara H, Oh H.
  • Journal Title: Mol Cell Biol. 28 Pages: 3424-3436
  • Peer Reviewed
• [Journal Article] MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis (2008)
  • Author(s): Tagawa M, Ueyama T, Ogata T, Takehara N, Nakajima N, Isodono K, Asada S, Takahashi T, Matsubara H, Oh H.
  • Journal Title: Am J Physiol Cell Physiol. 295
  • Peer Reviewed
• [Journal Article] Crossveinless-2 controls bone morphogenetic protein signaling during early cardiomyocyte differentiation in P19 cells (2008)
  • Author(s): Harada K, Ogai A, Takahashi T, Kitakaze M, Matsubara H, Oh H.
  • Journal Title: J Biol Chem. 283 Pages: 26705-26713
  • Peer Reviewed
• [Journal Article] Stemming heart failure with cardiac- or reprogrammed-stem cells (2008)
  • Author(s): Tateishi K, Takehara N, Matsubara H, Oh H.
  • Journal Title: J Cell Mol Med. 12 Pages: 2217-2232
  • Peer Reviewed
• [Journal Article] Downregulation of Dicer expression by serum withdrawal sensitizes human endothelial cells to apoptosis (2008)
  • Author(s): Asada S, Takahashi T, Isodono K, Adachi A, Imoto H, Ogata T, Ueyama T, Matsubara H, Oh H.
  • Journal Title: Am J Physiol Heart Circ Physiol. 295
  • Peer Reviewed
• [Journal Article] Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction (2008)
  • Author(s): Takahara N, Tsutsumi Y, Tateishi K, Ogata T, Tanaka H, Ueyama T, Takahashi T, Takamatau T, Fukushima M, Komeda M, Yamagishi M, Yaku H, Tabata Y, Matsubara H, Oh H.
  • Journal Title: J Am Coll Cardiol. 52 Pages: 1858-1865
  • Peer Reviewed
• [Presentation] A novel coiled-coil protein, MURC, for muscle growth (2010)
  • Author(s): 王英正
  • Organizer: テキサス大学医学部学術セミナー
  • Place of Presentation: ヒューストン
  • Year and Date: 2010-11-13
• [Presentation] Therapeutic Cardiac Stem Cell Project (2010)
  • Author(s): 王英正
  • Organizer: 第三回日仏トランスレーショナルリサーチ懇話会
  • Place of Presentation: 京都大学稲盛ホール
  • Year and Date: 2010-10-27
• [Presentation] Controlled Delivery of Basic Fibroblast Growth Factor Promotes Human Cardiac Stem Cell Engraftment and Differentiation to Enhance Cardiac Repair (2010)
  • Author(s): 王英正
  • Organizer: 2008 Catholic International Stem Cell Symposium
  • Place of Presentation: ソウル
  • Year and Date: 2010-06-20
• [Presentation] 重症心不全への幹細胞移植療法の臨床開発 (2010)
  • Author(s): 王英正
  • Organizer: 明石医師会学術講演会
  • Place of Presentation: 明石市医師会館
  • Year and Date: 2010-06-14
• [Presentation] Hybrid Stem Cell Therapy for Cardiac Repair (2010)
  • Author(s): Hidemasa Oh
  • Organizer: BIT's 3rd Annual Congress of Regenerative Medicine & Stem Cell-2010
  • Place of Presentation: Shanghai, China
  • Year and Date: 2010-06-12
• [Presentation] Controlled Delivery of Basic Fibroblast Growth Factor Promotes Human Cardiac Stem Cell Engraftment and Differentiation to Enhance Cardiac Repair (2010)
  • Author(s): 王英正
  • Organizer: 2008 Innovative Research Institute for Cell Therapy
  • Place of Presentation: ソウル
  • Year and Date: 2010-05-22
• [Presentation] Transplantation of autologous human cardiosphere-derived stem cellsinnovated via hydrogel surgical approach ; the first-in-man clinical trial. (2010)
  • Author(s): Takehara N, Tsutsumi Y, Amano K, Oh H, Yaku H, Tabata Y, Matsubara H
  • Organizer: XX World Congress of International Society for Heart Failure, 114
  • Place of Presentation: P-1-37-2
  • Year and Date: 2010-05-04
• [Presentation] 心筋再生医療が描く現在と未来 (2010)
  • Author(s): 王英正
  • Organizer: 2010年循環器エキスパート合同ミーティング
  • Place of Presentation: 岡山
  • Year and Date: 2010-04-12
• [Presentation] 小児心不全への細胞治療法の開発 (2010)
  • Author(s): 王英正
  • Organizer: 第16回西日本小児がんセミナー
  • Place of Presentation: 大阪
  • Year and Date: 2010-02-25
• [Presentation] 心血管再生医療の新たな臨床展開 (2009)
  • Author(s): 王英正
  • Organizer: 第15回岡山血流改善研究会
  • Place of Presentation: 岡山
  • Year and Date: 2009-11-05
• [Presentation] New Advances in Cardiac Cell Therapy. (2009)
  • Author(s): Oh H
  • Organizer: The 17th Asian Pacific Congress of Cardiology
  • Place of Presentation: Kyoto
  • Year and Date: 2009-05-23
• [Presentation] New Advances in Cardiac Cell Therapy. (2009)
  • Author(s): Oh H.
  • Organizer: The 17^<th> Asian Pacific Congress of Cardiology
  • Place of Presentation: Kyoto
  • Year and Date: 2009-05-16
• [Presentation] New Developments in Cardiac Cell Therapy (2009)
  • Author(s): 王英正
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-03-21
• [Presentation] Downregulation of Dicer Expression by Serum Withdrwal Snesiti'zes Human Endothelial Cells to Apoptosis (2009)
  • Author(s): 浅田聡
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-03-21
• [Presentation] Cell Therapy Improves Cardiac Dyssynchrony and Reduces the TransmuralExtent of Ischemic Regions in Chronic Myocardial Infarction (2009)
  • Author(s): 竹原有史
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-03-21
• [Presentation] Cardiac Regenerative Hybrid-therapy Integrated via Human Autologous cardiac Stem Cell and Biodegradable bFGF-incorporating Gelatin Hydrogel (2009)
  • Author(s): 竹原有史
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-03-21
• [Presentation] New Developments in Cardiac Cell Therapy. (2009)
  • Author(s): Oh H.
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-12
• [Presentation] Cell Therapy Improves Cardiac Dyssynchrony and Reduces the Transmural Extent of the Ischemic Regions in Chronic Myocardial Infarction. (2009)
  • Author(s): Takehara N, Amano K, Takahashi T, Kawabe J, Oh H, Yaku H, Tabata Y, Hasebe N, Matsubara H.
  • Organizer: 第73回 日本循環器学会総会学術集会,Circulation Journal 73;PJ-335
  • Year and Date: 2009-03-12
• [Presentation] Cardiac Regenerative Hybrid-thrapy Integrated via Human Autologous Cardiac Stem Cell and Biodegradable bFGF-incorporating Gelatin Hydrogel. (2009)
  • Author(s): Takehara N, Tsutsumi Y, Amano K, Takahshi T, Yaku H, Tabata Y, Oh H, Hasebe N, Matsubara H.
  • Organizer: 第73回 日本循環器学会総会学術集会Circulation Journal 73 ; SY-11-5
  • Year and Date: 2009-03-12
• [Presentation] A novel hybrid cell therapy for cardiac repair. (2008)
  • Author(s): Oh H.
  • Organizer: The 2nd Spring Cell Therapy Symposium
  • Place of Presentation: Korea
  • Year and Date: 2008-05-14
• [Presentation] 重症心不全に対する心臓内幹細胞の自家細胞移植による心筋再生医療 (2008)
  • Author(s): 王英正
  • Organizer: 秋桜会学術懇話会
  • Place of Presentation: 大阪
  • Year and Date: 2008-04-06
• [Presentation] ヒト心臓内幹細胞を用いた自家細胞移植による心筋再生医療 (2008)
  • Author(s): 王英正
  • Organizer: 第7回日本再生医療学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-18
• [Presentation] Human cardiac stem cell biotherapy integrated with bFGF controlled-release : Two randomized, dose-ranging, controlled preclinical trials (2008)
  • Author(s): Takehara N, Tabata Y, Tsutsumi Y, Matsubara H, Oh H.
  • Organizer: 第72回 日本循環器学会総会学術集会Circulation Journal 72 ; SY-12-3
  • Year and Date: 2008-03-15
• [Book] 心筋幹細胞(循環器科特集66) (2009)
  • Author(s): 王英正
• [Book] 新しい心臓再生法(Medical View Point) (2009)
  • Author(s): 王英正
• [Book] Cardiosphereによる心筋再生(分担)(Annual Review循環器) (2009)
  • Author(s): 竹原有史、服部玲治、松原弘明、王英正
  • Publisher: 中外医学社
• [Book] 再生医療 (2009)
  • Author(s): 中岡幹彦
  • Total Pages: 7
  • Publisher: メディカルビュー社
• [Book] Annual Review 循環器 (2009)
  • Author(s): 竹原有史
  • Total Pages: 8
  • Publisher: 中外医学社
• [Book] 総合臨床 (2009)
  • Author(s): 中西直彦
  • Total Pages: 8
  • Publisher: 永井書店
• [Book] 分子心血管病 (2009)
  • Author(s): 山口真一郎
  • Total Pages: 8
  • Publisher: 先端医学社
• [Book] 心臓内幹細胞の特性と自己複製制御機構(実験医学増刊号134) (2008)
  • Author(s): 王英正、立石健人、松原弘明
• [Book] 心臓組織内幹細胞を用いた心不全への心筋再生医療の現状 心電図28 (2008)
  • Author(s): 王英正
• [Book] Isl-1前駆細胞((Annual Review 循環器1) (2008)
  • Author(s): 王英正
  • Publisher: 中外医学社
• [Book] Medical View Point (2008)
  • Author(s): 王英正
  • Total Pages: 2
  • Publisher: 医事出版社
• [Remarks] ホームページ等
  • URL: http://shin-iryo.jp/
• [Remarks]
  • URL: http://cvs.icn.jp/shiniryo.html
• [Patent(Industrial Property Rights)] 細胞移植療法に用いられる心疾患治療薬 (2010)
  • Inventor(s): 王英正、竹原有史、松原弘明
  • Industrial Property Rights Holder: バイオマーかーサイエンス
  • Filing Date: 2010-10-09
• [Patent(Industrial Property Rights)] 細胞移植治療に用いられる心疾患治療薬 (2008)
  • Inventor(s): 王英正、竹原有史、田畑泰彦、松原弘明
  • Industrial Property Rights Holder: 京都大学
  • Filing Date: 2008-09-10
  • Overseas