2007 Fiscal Year Final Research Report Summary
Development of hybrid stem cell therapy for human heart failure
| Project/Area Number |
18390233
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 University |
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Principal Investigator |
OH Hidemasa Kyoto University, Dep. Experimental Therapeutic, Associate Professor (50372579)
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| Co-Investigator(Kenkyū-buntansha) |
UEYAMA Tomomi Kyoto University, Dep. Experimental Therapeutic, Assistant Professor (80379388)
HARADA Koichiro Kyoto University, Dep. Experimental Therapeutic, Assistant Professor (30402902)
OAGATA Takehiro Kyoto University, Dep. Experimental Therapeutic, Research Associate (10402877)
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| Project Period (FY) |
2006 – 2007
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| Keywords | cardiac stem cells / autologous transplantation / heart failure / stem cell growth factor / tissue engineering |
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| Research Abstract |
To develop an efficient cell therapy for cardiac repair, we performed serial analysis of gene expression and identified follistatin, an antagonist of TGF-β family members, was predominantly expressed in skeletal muscle-derived progenitors. We have found that follistatin may be an effective progenitor-enhancing agent neutralizing ActA and GDF11 signaling to regulate the growth of progenitor cells in skeletal muscle. In addition, we demonstrate a single-cell deposition analysis to isolate individually selected cardiac stem cells from adult hearts and investigate the signals required for their proliferation and survival. Clonally proliferated cardiac stem cells 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 enriched
… More
for cells expressing Sca-1. Knockdown of Sca-1 transcripts in cardiac stem cells led to retarded ex vivo expansion and apoptosis through Akt inactivation. We also show that ongoing cardiac stem cell 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 be an essential component that promotes cardiac stem cell proliferation and survival to directly facilitate early engraftment, and that indirectly exerts the effects on late cardiovascular differentiation after cardiac stem cell transplantation. Based on these observations in rodents, we conducted two randomized, placebo-controlled studies in immunosuppressed pigs with anterior myocardial infarctions. As the results of these studies, we found that controlled delivery of bFGF modulates the post-ischemic microenvironment to enhance human cardiac stem cell engraftment and differentiation. This novel integrated-strategy demonstrates significantly functional improvements after myocardial infarction and could be a potentially safe and feasible application to treat human heart failure. Less
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Research Products
(26 results)
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[Journal Article] MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance2008
Author(s)
Ogata, T., Ueyama, T., Isodono, K., Tagawa, M., Takehara, N., Kawashima, T., Harada, K., Takahashi, T., Shioi, T., Matsubara, H., Oh, H
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Journal Title
Mol Cell Biol 28
Pages: 3424-3436
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-beta family signaling2008
Author(s)
Nomura, T., Ueyama, T., Ashihara, E., Tateishi, K., Asada, S., Nakajima, N., Isodono, K., Takahashi, T., Matsubara H., Oh, H
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Journal Title
Biochem Biophys Res Commun 365
Pages: 863-869
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Therapeutic potential of stem/progenitor cells in human skeletal muscle for cardiovascular regeneration2007
Author(s)
Nomura, T., Ashihara, E., Tateishi, K., Ueyama, T., Takahashi, T., Yamagishi, M., Kubo, T., Yaku, H., Matsubara, H., Oh, H
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Journal Title
Current Stem Cell Research and Therapy 2
Pages: 293-300
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Endogenous Smad2 Activation Modulates Cardiac Differentiation in Embryonic Stem Cells2007
Author(s)
Kitamura, R., Takahashi, T., Nakajima, N., Isodono, K., Asada, S., Ueno, H., Ueyama, T., Matsubara, H., Oh, H
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Journal Title
Circ Res 101
Pages: 78-87
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway2007
Author(s)
Ogata, T., Ueyama, T., Nomura, T., Asada, S., Tagawa, M., Nakamura, T., Takahashi, T., Matsubara, H., Oh, H
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Journal Title
Biochem Biophys Res Commun 359
Pages: 341-347
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Single cardiac stem cells require stem cell antigen -1 to proliferate and survive for efficient cardiovascular regeneration2007
Author(s)
Tateishi, K., Ashihara, E., Takehara, N., Nomura, T., Honsho, S., Nagagami, T., Morikawa, S., Takahashi, T., Ueyama, T., Matsubara, H., Oh, H
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Journal Title
J Cell Sci 120
Pages: 1791-800
Description
「研究成果報告書概要(欧文)」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 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
Year and Date
2007-11-04
Description
「研究成果報告書概要(欧文)」より
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[Book] 分子血管病2007
Author(s)
王 英正
Total Pages
8
Publisher
先端医学社
Description
「研究成果報告書概要(和文)」より
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[Book] 呼吸と循環2007
Author(s)
王 英正
Total Pages
8
Publisher
医学書院
Description
「研究成果報告書概要(和文)」より
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