Human Cardiac Stem Cells With Reduced Notch Signaling Show Enhanced Therapeutic Potential in a Rat Acute Infarction Model
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概要
- 論文の詳細を見る
Background: Because human cardiac stem cells (CSC) have regeneration potential in damaged cardiac tissue, there is increasing interest in using them in cell-based therapies for cardiac failure. However, culture conditions, by which CSCs are expanded while maintaining their therapeutic potential, have not been optimized. We hypothesized that the plating cell-density would affect proliferation activity, differentiation and therapeutic potential of CSCs through the Notch signaling pathway. Methods and Results: Human CSCs were plated at 4 different densities. The population doubling time, C-KIT positivity, and dexamethasone-induced multidifferentiation potential were examined in vitro. The therapeutic potential of CSCs was assessed by transplanting them into a rat acute myocardial infarction (AMI) model. The low plating density (340cells/cm2) maintained the multidifferentiation potential with greater proliferation activity and C-KIT positivity in vitro. On the other hand, the high plating density (5,500cells/cm2) induced autonomous differentiation into endothelial cells by activating Notch signaling in vitro. CSCs cultured at low or high density with Notch signal inhibitor showed significantly greater therapeutic potential in vivo compared with those cultured at high density. Conclusions: CSCs cultured with reduced Notch signaling showed better cardiomyogenic differentiation and therapeutic potentials in a rat AMI model. Thus, reducing Notch signaling is important when culturing CSCs for clinical applications.
- 一般社団法人 日本循環器学会の論文
著者
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Asahara Takayuki
Vascular Regeneration Research Group, Institute of Biomedical Research and Innovation
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MIYAGAWA Shigeru
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine
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Saito Atsuhiro
Medical Center Of Translational Research Osaka University Hospital
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Sawa Yoshiki
Department Of Cardiovascular Medicine Osaka University Graduate School Of Medicine
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Fukushima Satsuki
Department Of Cardiovascular Surgery National Cardiovascular Center
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Matsuda Takenori
Department Of Orthopaedic Surgery Nara Medical University
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Asahara Takayuki
Vascular Regeneration Research Group
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Kitagawa-Sakakida Satoru
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine
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Akimaru Hiroshi
Vascular Regeneration Research Group, Institute of Biomedical Research and Innovation
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Horii-Komatsu Miki
Vascular Regeneration Research Group, Institute of Biomedical Research and Innovation
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Kawamoto Atsuhiko
Vascular Regeneration Research Group, Institute of Biomedical Research and Innovation
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Saito Atsuhiro
Medical Center for Translational Research, Osaka University Hospital
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