Elucidation of the mechanism of cardiac regeneration after transplantation of a complex of cardiac progenitor cells and nanofiber

• Project/Area Number: 22390156
• 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: Chiba University
• Principal Investigator: NAGAI TOSHIO 千葉大学, 医学(系)研究科(研究院), 准教授 (00334194)
• Co-Investigator(Kenkyū-buntansha): KOMURO Issei 東京大学, 大学院医学研究科, 教授 (30260483)
• Project Period (FY): 2010-04-01 – 2013-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
• Keywords: 分子心臓学 / 心臓前駆細胞 / 内在性心筋幹細胞 / 細胞移植 / パラクライン因子 / 心筋前駆細胞 / side population細胞 / DNA傷害 / 内在性心臓幹細胞 / 心臓side population細胞 / leukemia inhibitory factor / JAM-A

Research Abstract

Cardiac cell therapy has been proposed as one of the new strategies against heart failure; however, the mechanisms of the beneficial effects are largely unknown. We found that soluble junctional adhesion molecule-A (JAM-A), which is secreted from transplanted cardiac progenitor cells, prevent cardiac remodeling and reduce fibrosis area after myocardial infarction. In addition, by using a genetic fate-mapping model, we found that both leukemia inhibitory factor and transplantation of cardiac progenitor cells stimulate endogenous cardiomyocyte renewal after myocardial infarction.

Research Products

• [Journal Article] Gene and cytokine therapy for heart failure : molecular mechanisms in the improvement of cardiac function (2012)
  • Author(s): Nagai T, Komuro I
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 303
  • Peer Reviewed
• [Journal Article] Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes (2012)
  • Author(s): Naito AT, Sumida T, Nomura S, Liu ML, Higo T, Nakagawa A, Okada K, Sakai T, Hashimoto A, Hara Y, Shimizu I, Zhu W, Toko H, Katada A, Akazawa H, Oka T, Lee JK, Minamino T, Nagai T, Walsh K, Kikuchi A, Matsumoto M, Botto M, Shiojima I, Komuro I
  • Journal Title: Cell Volume: 149 Issue: 6 Pages: 1298-1313
  • DOI: 10.1016/j.cell.2012.03.047
  • Peer Reviewed
• [Journal Article] Gene and cytokine therapy for heart failure: molecular mechanisms in the improvement of cardiac function. (2012)
  • Author(s): Nagai T
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 303
  • Peer Reviewed
• [Journal Article] Urotensin II inhibits the proliferation but not the differentiation of cardiac side population cells (2011)
  • Author(s): Gong H, Ma H, Liu M, Zhou B, Zhang G, Chen Z, Jiang G, Yan Y, Yang C, Kanda M, Wu J, Yuan J, Li L, Nagai T, Komuro I, Ge J, Zou Y
  • Journal Title: Peptides Volume: 32 Issue: 5 Pages: 1035-1041
  • DOI: 10.1016/j.peptides.2011.01.024
  • Peer Reviewed
• [Journal Article] A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure (2011)
  • Author(s): Fukushima N1, Matsuura K, Akazawa H, Honda A, Nagai T, Takahashi T, Seki A, Murasaki KM, Shimizu T, Okano T, Hagiwara N, Komuro I
  • Journal Title: PLoS One Volume: 6(1371/journal.pone.0027901)
  • Peer Reviewed
• [Journal Article] A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure (2011)
  • Author(s): Fukushima N, Matsuura K, Akazawa H, Honda A, Nagai T, Takahashi T, Seki A, Murasaki KM, Shimizu T, Okano T, Hagiwara N, Komuro I
  • Journal Title: PLoS One Volume: 6 Issue: 12 Pages: e27901-e27901
  • DOI: 10.1371/journal.pone.0027901
  • Peer Reviewed
• [Journal Article] Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury (2010)
  • Author(s): Naito AT, Okada S, Minamino T, Iwanaga K, Liu ML, Sumida T, Nomura S, Sahara N, Mizoroki T, Takashima A, Akazawa H, Nagai T, Shiojima I, Komuro I
  • Journal Title: Circ Res Volume: 106 Issue: 11 Pages: 1692-1702
  • DOI: 10.1161/circresaha.109.214346
  • Peer Reviewed
• [Journal Article] Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction (2010)
  • Author(s): Tokunaga M, Liu ML, Nagai T, Iwanaga K, Matsuura K, Takahashi T, Kanda M, Kondo N, Wang P, Naito AT, Komuro I
  • Journal Title: JMol Cell Cardiol Volume: 49 Issue: 6 Pages: 972-983
  • DOI: 10.1016/j.yjmcc.2010.09.015
  • Peer Reviewed
• [Journal Article] Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury (2010)
  • Author(s): Naito AT
  • Journal Title: Circ Res Volume: 106 Pages: 1692-1702
  • Peer Reviewed
• [Journal Article] Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction (2010)
  • Author(s): Tokunaga M
  • Journal Title: J Mol Cell Cardiol Volume: 49 Pages: 972-983
  • Peer Reviewed
• [Presentation] 心臓の再生治療の可能性 (2013)
  • Author(s): 小室一成
  • Organizer: 第12回日本再生医療学会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-21
• [Presentation] The Effects of Leukemia Inhibitory Factor on Cardiac Stem Cell-derived Cardiomyocyte Renewal after Myocardial Infarction : A Genetic Fate-mapping Study (2012)
  • Author(s): Kanda M
  • Organizer: 第96回日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-18
• [Presentation] 内在性心筋幹/前駆細胞による心筋再生 (2012)
  • Author(s): 永井敏雄
  • Organizer: 日本心脈管作動物質学会シンポジウム
  • Place of Presentation: 秋田
  • Year and Date: 2012-02-10
• [Presentation] Anti-inflammatory Peptides S ecreted from Cardiac Progenitor Cells A meliorates Cardiac Dysfunction after My ocardial Infarction (2012)
  • Author(s): Liu ML
  • Organizer: American Heart Ass ociation 2012 Scientific Session
  • Place of Presentation: Los Angeles USA
• [Presentation] A Genetic Fate-Mapping Stud y Shows That Leukemia Inhibitory Factor Stimulates Cardiac Stem Cell-Derived C ardiomyocyte Renewal After Myocardial I nfarction (2012)
  • Author(s): Kanda M
  • Organizer: Basic Cardiovascular Science 2012 Scientific Sessions
  • Place of Presentation: New Orleans, USA
• [Presentation] Brown adipose tissue derived-cells differentiate into cardiac conduction and pace-maker cells in vitro and improve complete AV block in vivo (2012)
  • Author(s): Takahashi T
  • Organizer: International Society for Stem Cell Research 11^<th> Annyal Meeting
  • Place of Presentation: Yokohama, Japan
• [Presentation] Anti-inflammatory Peptides Secreted from Cardiac Progenitor Cells Ameliorates Cardiac Dysfunction after Myocardial Infarction. (2012)
  • Author(s): Liu ML
  • Organizer: American Heart Association 2012 Scientific Session
  • Place of Presentation: Los Angeles USA
• [Presentation] A Genetic Fate-Mapping Study Shows That Leukemia Inhibitory Factor Stimulates Cardiac Stem Cell-Derived Cardiomyocyte Renewal After Myocardial Infarction. (2012)
  • Author(s): Kanda M
  • Organizer: Basic Cardiovascular Science 2012 Scientific Sessions
  • Place of Presentation: New Orleans, USA
• [Presentation] Brown adipose tissue derived-cells differentiate into cardiac conduction and pace-maker cells in vitro and improve complete AV block in vivo. (2012)
  • Author(s): Takahashi T
  • Organizer: International Society for Stem Cell Research 11th Annyal Meeting
  • Place of Presentation: 横浜
• [Presentation] A Genetic Fate-Mapping Stud y Showing That Leukemia Inhibitory Fact or SimulatesCardiac Stem Cell-derived C ardiomyocyte Renewal After Myocardial I nfarction (2011)
  • Author(s): Kanda M
  • Organizer: Scientific Sessions 2011 Ame rican Heart Association
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2011-11-14
• [Presentation] A Genetic Fate-Mapping Study Showing That Leukemia Inhibitory Factor Simulates Cardiac Stem Cell-derived Cardiomyocyte Renewal After Myocardial Infarction (2011)
  • Author(s): Kanda M
  • Organizer: Scientific Sessions 2011 American Heart Association
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2011-11-14
• [Presentation] 内在性心筋幹細胞による心筋再生 (2011)
  • Author(s): 永井敏雄
  • Organizer: 第15回日本心不全学会学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2011-10-14
• [Presentation] 内在性心筋幹細胞による心筋再生 (2011)
  • Author(s): 永井敏雄
  • Organizer: 第15回日本心不全学会学術集会
  • Place of Presentation: 鹿児島(招待講演)
  • Year and Date: 2011-10-14
• [Presentation] Brown adipose tissue derived-cells differentiate into cardiac conduction and pace-maker cells in vitro and improve complete AV block in vivo (2011)
  • Author(s): Takahashi T
  • Organizer: 第95回日本循環器学会
  • Place of Presentation: 東京
  • Year and Date: 2011-08-03
• [Presentation] 体性幹細胞移植による心筋再生の機序 (2010)
  • Author(s): 永井敏雄
  • Organizer: 第13回小児心血管分子医学研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-08
• [Presentation] 体性幹細胞移植による心筋再生の機序 (2010)
  • Author(s): 永井敏雄
  • Organizer: 第13回小児心血管分子医学研究会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-07-08
• [Presentation] 体性組織幹細胞?心筋幹細胞と脂肪組織幹細胞による心筋再生 (2010)
  • Author(s): 永井敏雄
  • Organizer: 2010 Tokyo Heart Dev Club
  • Place of Presentation: 東京
  • Year and Date: 2010-04-09
• [Presentation] 体性組織幹細胞～心筋幹細胞と脂肪組織幹細胞による心筋再生 (2010)
  • Author(s): 永井敏雄
  • Organizer: 2010 Tokyo Heart Dev Club
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-04-09