Research on differentiation factor and niche for cardiac stem/progenitor cells

• Project/Area Number: 24659381
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• 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)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 分子心臓病態学 / 心筋幹/前駆細胞 / 心筋再生 / 心筋梗塞 / 自己組織化ナノペプチド / 細胞移植

Research Abstract

We generated alpha-MHCMerCreMer/CAG-CAT-LacZ mice to detect newly formed cardiomyocytes after myocardial infarction. We found that some of the new cardiomyocytes are derived from cardiac stem/progenitor cells after entering the cell cycle. Next we produced a three-dimensional thick scaffold, in which cardiac progenitor cells (CPC) were cultivated in combination with self-assembling peptide and transplanted CPC-scaffold on the surface of myocardial infarction area of alpha-MHCMerCreMer/CAG-CAT-LacZ mice. Transplantation of CPC-scaffold enhanced the formation of new cardiomyocytes. We dissected heart tissue sections by using a laser micro dissection system and then identified several proteins, which expressed exclusively in the transplanted heart.

Research Products

• [Journal Article] Cardiac side population cells and Sca-1-positive cells (2013)
  • Author(s): Nagai T, Matsuura K, Komuro I.
  • Journal Title: Methods Mol Biol Volume: 1036 Pages: 63-74
  • DOI: 10.1007/978-1-62703-511-8_5
  • ISBN: 9781627035101, 9781627035118
• [Journal Article] Notch activation mediates angiotensin II-induced vascular remodeling by promoting the proliferation and migration of vascular smooth muscle cells (2013)
  • Author(s): Ozasa Y, Akazawa H, Qin Y, Tateno K, Ito K, Kudo-Sakamoto Y, Yano M, Yabumoto C, Naito AT, Oka T, Lee JK, Minamino T, Nagai T, Kobayashi Y, Komuro I
  • Journal Title: Hypertens Res Volume: 36(10) Issue: 10 Pages: 859-65
  • DOI: 10.1038/hr.2013.52
  • 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 Pages: 1298-313
  • Peer Reviewed
• [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): 2. Nagai T
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 303 Issue: 5 Pages: H501-H512
  • DOI: 10.1152/ajpheart.00130.2012
  • Peer Reviewed
• [Presentation] 細胞動員の制御による心臓修復治療 (2014)
  • Author(s): 李鍾國
  • Organizer: 第13回日本再生医療学会
  • Place of Presentation: 京都
• [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] 心筋再生治療の可能性 (2013)
  • Author(s): 永井敏雄
  • Organizer: 第17回日本心不全学会
  • Place of Presentation: 大宮
• [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総会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Invited
• [Presentation] Pericardial grafting of cardiac progenitor cells in the Three-dimentional thick scaffold improves cardiac function after myocardial infarction. (2013)
  • Author(s): Kondo N
  • Organizer: The 77th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: パシフィコ横浜 （神奈川県）
• [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] Leukemia Inhibitory Factor (LIF)は心筋幹細胞の増殖をうながし、心筋梗塞後における心筋再生を促進する (2012)
  • Author(s): 神田真人
  • Organizer: 第33回日本炎症・再生医学会
  • Place of Presentation: 福岡
• [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: 横浜
• [Presentation] Leukemia Inhibitory Factor (LIF)は心筋幹細胞の増殖を介し、心筋梗塞後における心筋再生を促進する (2012)
  • Author(s): 神田真人
  • Organizer: 第49回日本臨床分子医学会学術集会YIA
  • Place of Presentation: 京都
• [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 10th Annual Meeting
  • Place of Presentation: パシフィコ横浜 （神奈川県）
• [Presentation] Leukemia Inhibitory Factor Administration Enhances Endogenous Cardiomyocytes Regeneration after Myocardial Infarction by Activating Cardiac Side Population cells : A Genetic Fate-mapping Study (2012)
  • Author(s): Kanda M
  • Organizer: International Society for Stem Cell Research 10th Annual Meeting
  • Place of Presentation: パシフィコ横浜 （神奈川県）
• [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: Hilton New Orleans Riverside New Orleans, USA
• [Presentation] Anti-inflammatory Peptides Secreted from Cardiac Progenitor Cells Ameliorates Cardiac Dysfunction after Myocardial Infarction. (2012)
  • Author(s): Mei-Lan Liu
  • Organizer: 米国心臓病会議2012
  • Place of Presentation: ロサンゼルスコベンションセンター（米国））
• [Presentation] Leukemia Inhibitory Factor (LIF)は心筋幹細胞の増殖を介し、心筋梗塞後における心筋再生を促進する (2012)
  • Author(s): 神田真人
  • Organizer: 第49回日本臨床分子医学会学術集会
  • Place of Presentation: みやこめっせ （京都府）
• [Presentation] Leukemia Inhibitory Factor (LIF)は心筋幹細胞の増殖をうながし、心筋梗塞後における心筋再生を促進する (2012)
  • Author(s): 神田真人
  • Organizer: 第33回 日本炎症・再生医学会
  • Place of Presentation: ホテル日航福岡 （福岡県）
• [Presentation] 自己組織化ナノペプチドを用いた厚肉心筋前駆細胞移植床による心筋梗塞治療
  • Author(s): 近藤尚通
  • Organizer: 第2回心臓先端医療研究会
  • Place of Presentation: 千里阪急ホテル （大阪府）