2007 Fiscal Year Final Research Report Summary
Cardiac Repair of Severe Heart Failure by Human Heart- or Skeletal Muscle-Derived Multipotent Stem Cells
| Project/Area Number |
17209028
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
MATSUBARA Hiroaki Kyoto Prefectural University of Medicine, School of Medicine Department of Medicine, Professor (10239072)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Tomosaburo Kyoto Prefectural University School of Medicine, Department of Medicine, Instructor (20381973)
OH Hidemasa Kyoto University, Department of Medicine, Associate Professor (50372579)
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| Project Period (FY) |
2005 – 2007
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| Keywords | cardiac stem cell / heart failure / regeneration / cardiomyogenesis |
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| Research Abstract |
Recent studies have shown that cardiac stem cells (CSCs) from the adult heart can give rise to functional cardiomyocytes; however, the definite surface markers to identify a definitive single entity of CSCs and the molecular mechanisms regulating their growth have remained unknown. Here we demonstrate a single-cell deposition analysis to isolate individually selected CSCs from adult hearts and investigate the signals required for their proliferation and survival. Clonally proliferated CSCs express stem cell antigen-1 (Sca-1) with embryonic stem (ES) cell-and mesenchymal cell-like characteristics and are associated with telomerase reverse transcriptase (TERT). Using a transgene that expresses a GFP reporter under the control of the TERT promoter, we demonstrated that TERT^<GFP+> fractions from the heart were entiched for cell expressing Sca-1. Knockdown of Sca-1 transcripts in CSCs led to retarded ex vivo expansion and apoptosis through Akt inactivation. We also show that ongoing CSC proliferation and survival after direct cell-grafting into ischemic myocardium require Sca-1 to upregulate the secreted paracrine effectors that augment neoangiogenesis and limit cardiac apoptosis, Thus, Sca-1 might bean essential component that promotes CSC proliferation and survival to directly facilitate early engraftment, and that indirectly exerts the effects on late cardiovascular differentiation after CSC transplantation.
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Research Products
(102 results)
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[Presentation] Overexpression of Tie2-promoted Activated Fibroblast Growth Factor Receptor 2 in Endothelial Cells enhances Angiogenesis and Induces Cardioprotective Effect via Src-Akt-Hiflα Signaling Pathway in Mice Myocardial Infarction2007
Author(s)
Matsunaga S, Tatsumi T, Okigaki M, Kishita E, Kimata M, Honsyo S, Takeda M, Nishikawa S, Matoba S, Kobara M, Matsubara H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Orlando,USA
Year and Date
20071104-07
Description
「研究成果報告書概要(和文)」より
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[Presentation] Controlled Intramyocardial-delivery of Basic Fibroblast Growth Factor Combined With Human Cardiac Stem Cell Transplantation In Chronic Myocardial Infarction:A Randomized Controlled Preclillical-trial.2007
Author(s)
Takehaza N, Tsutsuymi Y, Ota H, Tateishi K, Takahashi T, Ueyama T, Yamagishi M, Yaku H, Tabata Y, Matsubara H, Oh H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Orlando,USA
Year and Date
20071104-07
Description
「研究成果報告書概要(和文)」より
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[Presentation] Bone Marrow Angiotensin AT1 and AT2 Receptors Differentially Modulate Vascular Repair by Regulating Mobilization and Activation of Bone Marrow-Derived Vascular Progenitors2007
Author(s)
Yokoi H, Yamada H, Tsubakimoto Y, Takata H, Kawahito H, Takahashi T, Okigaki M, Hirai H, Ahihara E, Maekawa T, Iwai M, Horiuchi M, Matsubara H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Orlando,USA
Year and Date
20071104-07
Description
「研究成果報告書概要(和文)」より
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[Presentation] Mild Renal Dysfunction Caused by Uninephrectomy Accelerated the Development of Atherosclerosis by Augmented Monocyte Mobilization from Bone Marrow via CCR2-Mediated Signals2007
Author(s)
Kawahito H, Yamada H, Tsubakimoto Y, Yokoi H, Takata H, Hirai H, Imanishi J, Takahashi T, Okigaki M, Mori Y, Matsubara H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Orlando,USA
Year and Date
20071104-07
Description
「研究成果報告書概要(和文)」より
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[Presentation] Bone Marrow Angiotensin Type1 Receptor Augments Atherosclerosis by Promoting Monocyte/Macrophage Lineage Differentiation form Hematopoietic Stem Cells2007
Author(s)
Tsubakimoto Y, Yamada H, Yokoi H, Takata H, Kawahito H, Hirai H, Imanishi J, Ashihara E, Maekawa T, Takahashi T, Okigaki M, Matsubara H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Orlando,USA
Year and Date
20071104-07
Description
「研究成果報告書概要(和文)」より
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[Presentation] Cardioprotective Action of Interleukin-13 in Adaptation to Cardiac Pressure Overload Stress by Activation of IGF-1 /Akt Pathway2007
Author(s)
Honsho, S., Nisikawa, S., Kishita, E., Katsume, A., Matsunaga, S., Matsui, A., Okigaki M., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] p53 Shifts the Balance of Energy Source in Cardiac Myocytes2007
Author(s)
Kimata, M., Matoba, S., Nakamura, H., Tatsumi, T., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Ca2+-dependent Tyrosine Kinase PYK2 Promotes Atherougenesis by Inducing Monocyte and endothelial cell-Derived TNF-alpha and MCP-1 Synthesis Unmasked by Analysis of PYK2/ApoE Double Deficient Mice2007
Author(s)
Katsume, A., Okigaki, M., Matsui, A., Yamada, H., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Controlled Intramyocardial-delivery of Basic Fibroblast Growth Factor Combined With Human Cardiac Stem Cell Transplantation In Chronic Myocardial Infarction: A Randomized Controlled Preclinical-trial2007
Author(s)
Takehara, N., Tsutsumi, Y., Ota, H., Tateishi, K., Takahashi, T., Ueyama, T., Yamagishi M., Yaku, H., Tabata, Y., Matsubara, H., Oh, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Myocardin is Required to Prevent Mitochondorial Damage and Cardiac Dysfunction in Response to Beta-Adrenergic Receptor Stimulation2007
Author(s)
Kobayashi, S., Ueyama, T., Roh, R., Masano, T., Sakoda, T., Matsubara, H., Oh, H., Hirata, K
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Bone Marrow Angiotensin AT1 and AT2 Receptors Differentially Modulate Vascular Repair by Regulating Mobilization and Activation of Bone Marrow-Derived Vascular Progenitors2007
Author(s)
Yokoi, H., Yamada, H., Tsubakimoto, Y., Takata, H., Kawahito, H., Takahashi, T., Okigaki, M., Hirai, H., Ahihara, E., Maekawa, T., Iwai, M., Horiuchi, M., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Central Role of Calcium-Dependent Tyrosine Kinase PYK2 in eNOS-Mediated Vascular Function and Angiogenic Response- Unmasked by PYK2 Knockout Mice-2007
Author(s)
Matsui, A., Okigaki, M., Katsume, A., Matsunaga, S., Yamada, H., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Klotho-protein Regulates Transient Receptor Potential Canonimal-l-mediated Ca(2+)-influx In Endothelial Cells And Prevents Cell Death And Disruption Of Endothelial Integrity Induced By Ca(2+)-overlaod2007
Author(s)
Okigaki, M., Kusaba, T., Honsyo, S., Matsui, A., Matsunaga, S., Katsume, A., Kishita, E., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Calcium-Dependent Tyrosine Kinase PYK2 Plays Crucial Role it Angiotensin ^- But Not Norepineprine-Mediated Activation of Rac/Superoxide Pathway That Differentially Regulates Blooc Pressure and Vasoconstriction2007
Author(s)
Matsui, A., Okigaki, M., Katsume, A., Yamada, H., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Mild Renal Dysfunction Caused by Uninephrectomy Accelerated the Development of Atherosclerosis by Augmented Monocyte Mobilization from Bone Marrow via CCR2-Mediated Signals2007
Author(s)
Kawahito, H., Yamada, H., Tsubakimoto, Y., Yokoi, H., Takata, H., Hirai, H., Imanishi, J., Takahashi, T., Okigaki, M., Mori, Y., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Overexpression of Tie2-promoted Activated Fibroblast Growth Factor Receptor 2 in Endothelial Cells enhances Angiogenesis and Induces Cardioprotective Effect via Src-Akt-Hifla Signaling Pathway in Mice Myocardial Infarction2007
Author(s)
Matsunaga, S., Tatsumi, T., Okigaki, M., Kishita, E., Kimata, M., Honsyo, S., Takeda, M., Nishikawa, S., Matoba, S., Kobara, M., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Bone Marrow Angiotensin ^ Typel Receptor Augments Atherosclerosis by Promoting Monocyte/Macrophage Lineage Differentiation form Hematopoietic Stem Cells2007
Author(s)
Tsubakimoto, Y., Yamada, H. Yokoi, H., Takata, H., Kawahito, H., Hirai, H., Imanishi, J., Ashihara, E., Maekawa, T., Takahashi, T., Okigaki, M., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Orlando, USA
Year and Date
20071104-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Bone Marrow Cells that Abundantly Express Angiotensin AT1 and AT2 Receptors Modulate Vascular Repair by Regulating Mobilization and Differentiation of Smooth Muscle Cell Progenitors and Macrophage Activation2006
Author(s)
Yamada H, Yokoi H, Tsubakimoto Y, Takada H, Takahashi T, Okigaki M, Ashihara E, Maekawa T, Iwai M, Horiuchi M, Matsubara H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Chicago,USA
Year and Date
20061112-15
Description
「研究成果報告書概要(和文)」より
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[Presentation] Overexpression of Tie2-Promoted Activated Fibroblast Growth Factor Receptor 2 in Endothelial Cells Enhances Mature Neovascularization via Akt Signaling Pathway in Mice Hindlimb Ischemia2006
Author(s)
Takeda, M., Tatsumi, T., Okigaki, M., Matsunaga, S., Nishikawa, S., Kobara, M., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Overexpression of Tie2-Promoted Activated Fibroblast Growth Factor Receptor 2 in Endothelial Cells Enhances Angiogenesis and Induces Cardioprotective Effect via Akt Signaling Pathway in Mice Myocardial Infarction.2006
Author(s)
Matsunaga, S., Tatsumi, T., Okigaki, M., Takeda, M., Nishikawa, S., Kobara, M., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Ca^<2+>-dependent Tyrosine Kinase PYK2 PromotesAtherogenesis by Inducing Monocyte/Macrophage-Derived IL-113 and MCP-1 Unmasked by Analysis of PYK2/ApoE Double Deficient Mice2006
Author(s)
Katsume, A., Okigaki, M., Matsui, A., Urao, N., Yamada, H., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Calcium-Dependent Tyrosine Kinase PYK2 Plays Crucial Role in Angiotensin II- But Not Norepineprine-Mediated Activation of Rac/Superoxide Pathway That Differentially Regulates Blood Pressure and Vasoconstriction Unmasked by Analysis of PYK2-Knock-out Mice.2006
Author(s)
Matsui, A., Okigaki, M., Katsume, A., Urao, N., Yamada, H., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Central Role of Calcium-Dependent Tyrosine Kinase PYK2 in eNOS-Mediated Angiogenesis Unmasked by PYK2 Knockout Mice2006
Author(s)
Matsui, A., Okigaki, M., Katsume, A., Matsunaga, S., Nishikawa, S., Urao, N., Yamada, H., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Antagonism of Interleukin-6 Receptor Attenuates Cardiac Remodeling After Myocardial Infarction2006
Author(s)
Kobara, M., Hamada, J., Matsumura, M., Tanaka, T., Toba, H., Hayashi, H., Tatsumi, T., Matsubara, H., Nakata, T
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] MicroRNA-1 Facilitates Myogenic Differentiation and Maturation into Skeletal Myotubes without Affecting Osteoblastic and Adipogenic Differentiation2006
Author(s)
Nakajima, N., Takahashi, T., Kitamura, R., Isodono, K., Asada, S., Ueyama, T., Matsubara, H., Oh, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Oh Single Cardiac Stem Cells in Adult Mammals Exhibit Mesenchymal Features and Proliferate through Akt/GSK3 Pathway2006
Author(s)
Tateishi, K., Takahshi, T., Honsho, S., Takehara, N., Nomura, T., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
-
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[Presentation] Bone Marrow Cells that Abundantly Express Angiotensin AT1 and AT2 Receptors Modulate Vascular Repair by Regulating Mobilization and Differentiation of Smooth Muscle Cell Progenitors and Macrophage Activation2006
Author(s)
Yamada, H., Yokoi, H., Tsubakimoto, Y., Takada, H., Takahashi, T., Okigaki, M., Ashihara, E., Maekawa, T., Iwai, M., Horiuchi, M., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Bone Marrow Angiotensin II Type 1 Receptor Accelerated the Development of Atherosclerosis by Regulating Differentiation of Macrophage Progenitors and Macrophage Functions2006
Author(s)
Yamada, H., Tsubakimoto, Y., Yokoi, H., Takada, H., Takahashi, T., Okigaki, M., Ashihara, E., Maekawa, T., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Single cardiac stem cells from adult mammalian heart are multipotent and can regenerate ischemic myocardium2006
Author(s)
Tateishi, K., Takahashi, T., Nomura, T., Matsubara, H., Oh, H
Organizer
American Heart Association
Place of Presentation
Chicago, USA
Year and Date
20061112-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] G-CSF Treatment Inhibits Neointimal Hyperplasia Associated with Endoth elial Progenitor Cell Mobilization and Acceleration of Reendothelialization in Catorid Artery injuty Model2005
Author(s)
Takamiya M, Okigaki M, Irie H, Zen K, Dohue T, Sawada T, Azuma A, Denan J, Takai S, Miyazaki M, Matsubara H
Organizer
American Heart Association(米国心臓病学術会議)
Place of Presentation
Dallas,USA
Year and Date
20051113-16
Description
「研究成果報告書概要(和文)」より
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[Presentation] G-CSF Treatment Inhibits Neointimal Hyperplasia Associated with Endothelial Progenitor Cell Mobilization and Acceleration of Reendothelialization in Catorid Artery Injuty Model2005
Author(s)
Takamiya, M., Okigaki, M., Irie, H., Zen, K., Dohue, T., Sawada, T., Azuma, A., Denan, J., Takai, S., Miyazaki, M., Matsubara, H
Organizer
American Heart Association
Place of Presentation
Dallas, USA
Year and Date
20051113-16
Description
「研究成果報告書概要(欧文)」より
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[Book] 血管疾患を知る2005
Author(s)
辰巳 哲也、松原 弘明
Total Pages
4(296)
Publisher
メジカルビュー社
Description
「研究成果報告書概要(和文)」より
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[Book] 医学書院2005
Author(s)
松原 弘明
Total Pages
2(2014)
Publisher
今日の治療指針
Description
「研究成果報告書概要(和文)」より
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