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

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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.