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シミズ タツヤ
SHIMIZU Tatsuya
清水 達也 所属 研究施設 研究施設 職種 教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Functional Evaluation of Human Bioengineered Cardiac Tissue Using iPS Cells Derived from a Patient with Lamin Variant Dilated Cardiomyopathy. |
| 掲載誌名 | 正式名：International heart journal 略 称：Int Heart J ISSNコード：13493299/13492365 |
| 掲載区分 | 国内 |
| 巻・号・頁 | 63(2),pp.338-346 |
| 著者・共著者 | MIURA Koichiro†, MATSUURA Katsuhisa*, YAMASAKI Itoyama Yu, SASAKI Daisuke, TAKADA Takuma, FURUTANI Yoshiyuki, HAYAMA Emiko, ITO Masamichi, NOMURA Seitaro, MORITA Hiroyuki, TOYODA Masashi, UMEZAWA Akihiro, ONOUE Kenji, SAITO Yoshihiko, ABURATANI Hiroyuki, NAKANISHI Toshio, HAGIWARA Nobuhisa, KOMURO Issei, SHIMIZU Tatsuya |
| 担当区分 | 最終著者 |
| 発行年月 | 2022/03/30 |
| 概要 | 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. |
| DOI | 10.1536/ihj.21-790 |
| PMID | 35354754 |