Analysis of the origin of newly formed cardiomyocytes and their growth and mitotic factor by cardiac progenitor cell scaffold transplantation model.

• Project/Area Number: 25293180
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular 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): 小室 一成 東京大学, 医学部附属病院, 教授 (30260483)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: 心筋前駆細胞 / DNA傷害 / 細胞移植床 / 心筋再生 / パラクライン効果 / side population細胞 / 細胞移植

Outline of Final Research Achievements

Activation and subsequent induction into cardiomyocytes differentiation of endogenous cardiac stem or progenitor cells is a new strategy for cardiac regeneration. We examined the mechanisms of endogenous cardiac regeneration after epicardial engraftment of cardiac progenitor cell (CPC) scaffold. Transplantation of CPC scaffold reduced the DNA damage of cardiac side population cells. CPC scaffold secreted the several factors that promote angiogenesis, inhibit apoptotic cell death, or reduce emigration of neutrophils. Transplantation of CPC scaffold preserved the expression of aldehyde dehydrogenase 2 in the injured heart. We established a multi colored mouse heart model for lineage tracing. By using this model we quantified the dynamics of cardiomyocyte division after myocardial injury.

Research Products

• [Journal Article] Leukemia Inhibitory Factor Enhances Endogenous Cardiomyocyte Regeneration after Myocardial Infarction. (2016)
  • Author(s): Kanda M, Nagai T, Takahashi T, Liu ML, Kondou N, Naito AT, Akazawa H, Sashida G, Iwama A, Komuro I, Kobayashi Y.
  • Journal Title: Plos One Volume: 11 Issue: 5 Pages: e0156562-e0156562
  • DOI: 10.1371/journal.pone.0156562
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regeneration of the Cardiac Conduction System by Adipose Tissue-Derived Stem Cells (2015)
  • Author(s): Takahashi T, Nagai T, Kanda M, Liu ML, Kondo N, Naito AT, Ogura T, Nakaya H, Lee JK, Komuro I, Kobayashi Y.
  • Journal Title: Circulation Journal Volume: 79 Issue: 12 Pages: 2703-2712
  • DOI: 10.1253/circj.CJ-15-0400
  • NAID: 130005110933
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling. (2015)
  • Author(s): Sumida T, Naito AT, Nomura S, Nakagawa A, Higo T, Hashimoto A, Okada K, Sakai T, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Minamino T, Offermanns S, Noda T, Botto M, Kobayashi Y, Morita H, Manabe I, Nagai T, Shiojima I, Komuro I.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 6241-6241
  • DOI: 10.1038/ncomms7241
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial aldehyde dehydrogenase 2 plays protective roles in heart failure after myocardial infarction via suppression of the cytosolic JNK/p53 pathway in mice. (2014)
  • Author(s): Sun A, Zou Y, Wang P, Xu D, Gong H, Wang S, Qin Y, Zhang P, Chen Y, Harada M, Isse T, Kawamoto T, Fan H, Yang P, Akazawa H, Nagai T, Ping P, Komuro I, Ge J.
  • Journal Title: J Am Heart Assoc Volume: 3 Issue: 5
  • DOI: 10.1161/jaha.113.000779
  • Peer Reviewed / Open Access
• [Journal Article] Anti-inflammatory peptides from cardiac progenitors ameliorate dysfunction after myocardial infarction. (2014)
  • Author(s): Liu ML, Nagai T, Tokunaga M, Iwanaga K, Matsuura K, Takahashi T, Kanda M, Kondo N, Naito AT, Komuro I, Kobayashi Y.
  • Journal Title: J Am Heart Assoc Volume: 3 Issue: 6
  • DOI: 10.1161/jaha.114.001101
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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
• [Presentation] Novel Multicolor Lineage Tracing Model Can Detect Cardiomyocyte-Derived Cardiac Regeneration after Injury. (2016)
  • Author(s): Kanda M, Nagai T, Takahashi T, Liu M, Kondou N, Naito A, Akazawa H, Komuro I, Kobayashi Y.
  • Organizer: 第80回日本循環器学会総会・学術集会
  • Place of Presentation: 仙台国際センター, 宮城県, 仙台市
  • Year and Date: 2016-03-17
• [Presentation] A Novel Multicolor Lineage Tracing Model Can Detect Cardiomyocyte-Derived Cardiac Regeneration After Myocardial Infarction. (2015)
  • Author(s): Kanda M, Nagai T, Takahashi T, Liu M, Kondou N, Naito A, Akazawa H, Komuro I, Kobayashi Y.
  • Organizer: American Heart Association Scientific Sessions 2015
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Leukemia Inhibitory Factor Enhances Cardiomyocyte Regeneration after Myocardial Infarction from Endogenous stem Cells and not from Circulating Bone Marrow-derived Cells. (2015)
  • Author(s): Kanda M, Nagai T, Takahashi T, Liu M, Kondou N, Naito A, Akazawa H, Komuro I, Kobayashi Y.
  • Organizer: European Society of Cardiology Congress 2015
  • Place of Presentation: London, UK
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [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
  • Invited
• [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
  • Invited