Regeneration of the Cardiac Conduction System by Adipose Tissue-Derived Stem Cells
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- Takahashi Toshinao
- Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
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- Nagai Toshio
- Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
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- Kanda Masato
- Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
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- Liu Mei-Lan
- Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
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- Kondo Naomichi
- Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
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- Naito Atsuhiko T
- Department of Cardiovascular Medicine, The University of Tokyo Hospital
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- Ogura Takehiko
- Department of Pharmacology, Chiba University Graduate School of Medicine
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- Nakaya Haruaki
- Department of Pharmacology, Chiba University Graduate School of Medicine
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- Lee Jong-Kook
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine
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- Komuro Issei
- Department of Cardiovascular Medicine, The University of Tokyo Hospital
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- Kobayashi Yoshio
- Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
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Abstract
Background:Adipose tissue is one of the sources of mesenchymal stem cells, which have the potential to differentiate into various types of cells, including myocytes. Whether brown adipose tissue (BAT)-derived cells might differentiate into the cardiac pacemaking-conducting cells, and have the potential to regenerate the cardiac conduction system (CCS), is investigated in this study.Methods and Results:BAT was isolated from the interscapular area of mice and enzymatically digested before culture. Round or fusiform cells showed spontaneous beating at 4–7 days after culturing of BAT-derived cells. Reverse transcriptase-polymerase chain reaction analysis and immunocytochemical analysis revealed that BAT-derived cells expressed several cardiomyocytes, the CCS and pacemaker (PM) cell marker genes and proteins. Patch-clamp techniques revealed that spontaneous electrical activity and the shape of the action potential showed properties of cardiac PM cells. Next, a complete atrioventricular (AV) block was created in mice and green fluorescent protein-positive (GFP (+)) BAT-derived cells were injected intramyocardially around the AV node. At 1 week after transplantation, 50% of BAT-derived cells injected mice showed a sinus rhythm or a 2:1 AV block. Immunohistochemical analysis revealed that injected GFP (+) cells were engrafted and some GFP (+) cells co-expressed several cardiac PM cell marker proteins.Conclusions:BAT-derived cells differentiate into the CCS and PM-like cells in vitro and in vivo, and may become a useful cell source for arrhythmia therapy. (Circ J 2015; 79: 2703–2712)
Journal
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- Circulation Journal
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Circulation Journal 79 (12), 2703-2712, 2015
The Japanese Circulation Society
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Details 詳細情報について
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- CRID
- 1390282680083070080
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- NII Article ID
- 130005110933
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- NII Book ID
- AA11591968
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- ISSN
- 13474820
- 13469843
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- NDL BIB ID
- 026944673
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- PubMed
- 26411528
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed