- 著者
- Koichiro Miura Katsuhisa Matsuura Yu Yamasaki Itoyama Daisuke Sasaki Takuma Takada Yoshiyuki Furutani Emiko Hayama Masamichi Ito Seitaro Nomura Hiroyuki Morita Masashi Toyoda Akihiro Umezawa Kenji Onoue Yoshihiko Saito Hiroyuki Aburatani Toshio Nakanishi Nobuhisa Hagiwara Issei Komuro Tatsuya Shimizu
- 出版者
- International Heart Journal Association
- 雑誌
- International Heart Journal (ISSN:13492365)
- 巻号頁・発行日
- vol.63, no.2, pp.338-346, 2022-03-30 (Released:2022-03-30)
- 参考文献数
- 35
- 被引用文献数
- 5
Dilated cardiomyopathy (DCM) is caused by various gene variants and characterized by systolic dysfunction. Lamin variants have been reported to have a poor prognosis. Medical and device therapies are not sufficient to improve the prognosis of DCM with the lamin variants. Recently, induced pluripotent stem (iPS) cells have been used for research on genetic disorders. However, few studies have evaluated the contractile function of cardiac tissue with lamin variants. The aim of this study was to elucidate the function of cardiac cell sheet tissue derived from patients with lamin variant DCM. iPS cells were generated from a patient with lamin A/C (LMNA) -mutant DCM (LMNA p.R225X mutation). After cardiac differentiation and purification, cardiac cell sheets that were fabricated through cultivation on a temperature-responsive culture dish were transferred to the surface of the fibrin gel, and the contractile force was measured. The contractile force and maximum contraction velocity, but not the maximum relaxation velocity, were significantly decreased in cardiac cell sheet tissue with the lamin variant. A qRT-PCR analysis revealed that mRNA expression of some contractile proteins, cardiac transcription factors, Ca2+-handling genes, and ion channels were downregulated in cardiac tissue with the lamin variant.Human iPS-derived bioengineered cardiac tissue with the LMNA p.R225X mutation has the functional properties of systolic dysfunction and may be a promising tissue model for understanding the underlying mechanisms of DCM.
- 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.