- 著者
- Toshinao Takahashi Toshio Nagai Masato Kanda Mei-Lan Liu Naomichi Kondo Atsuhiko T Naito Takehiko Ogura Haruaki Nakaya Jong-Kook Lee Issei Komuro Yoshio Kobayashi
- 出版者
- The Japanese Circulation Society
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- vol.79, no.12, pp.2703-2712, 2015-11-25 (Released:2015-11-25)
- 参考文献数
- 42
- 被引用文献数
- 7 17
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)
- 著者
- Taku Sakai Atsuhiko T. Naito Yuki Kuramoto Masamichi Ito Katsuki Okada Tomoaki Higo Akito Nakagawa Masato Shibamoto Toshihiro Yamaguchi Tomokazu Sumida Seitaro Nomura Akihiro Umezawa Shigeru Miyagawa Yoshiki Sawa Hiroyuki Morita Jong-Kook Lee Ichiro Shiojima Yasushi Sakata Issei Komuro
- 出版者
- International Heart Journal Association
- 雑誌
- International Heart Journal (ISSN:13492365)
- 巻号頁・発行日
- pp.17-730, (Released:2018-08-11)
- 参考文献数
- 28
- 被引用文献数
- 13
Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by hypertrophy of the myocardium. Some of the patients are diagnosed for HCM during infancy, and the prognosis of infantile HCM is worse than general HCM. Nevertheless, pathophysiology of infantile HCM is less investigated and remains largely unknown. In the present study, we generated induced pluripotent stem cells (iPSCs) from two patients with infantile HCM: one with Noonan syndrome and the other with idiopathic HCM. We found that iPSC-derived cardiomyocytes (iPSC-CMs) from idiopathic HCM patient were significantly larger and showed higher diastolic intracellular calcium concentration compared with the iPSC-CMs from healthy subject. Unlike iPSC-CMs from the adult/adolescent HCM patient, arrhythmia was not observed as a disease-related phenotype in iPSC-CMs from idiopathic infantile HCM patient. Phenotypic screening revealed that Pyr3, a transient receptor potential channel 3 channel inhibitor, decreased both the cell size and diastolic intracellular calcium concentration in iPSC-CMs from both Noonan syndrome and idiopathic infantile HCM patients, suggesting that the target of Pyr3 may play a role in the pathogenesis of infantile HCM, regardless of the etiology. Further research may unveil the possibility of Pyr3 or its derivatives in the treatment of infantile HCM.