日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Online ISSN: 2187-2988 Print ISSN: 0911-1794
特定非営利活動法人日本小児循環器学会 Japanese Society of Pediatric Cardiology and Cardiac Surgery
〒162-0801東京都新宿区山吹町358-5アカデミーセンター Japanese Society of Pediatric Cardiology and Cardiac Surgery Academy Center, 358-5 Yamabuki-cho, Shinju-ku, Tokyo 162-0801, Japan
Pediatric Cardiology and Cardiac Surgery 31(4): 138-147 (2015)
doi:10.9794/jspccs.31.138

ReviewReview

疾患特異的iPS細胞を用いた先天性心疾患の病態解明Congenital Heart Diseases and Disease-specific iPS Cells

1岡山大学大学院医歯薬学総合研究科心臓血管外科学教室Department of Cardiovascular Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ◇ 〒700-8558 岡山県岡山市北区鹿田町二丁目5番1号2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan

2岡山大学病院新医療研究開発センター再生医療部Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital ◇ 〒700-8558 岡山県岡山市北区鹿田町二丁目5番1号2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan

受付日:2015年1月22日Received: January 22, 2015
受理日:2015年5月22日Accepted: May 22, 2015
発行日:2015年7月1日Published: July 1, 2015
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2007年にヒト人工多能性幹(induced pluripotent stem: iPS)細胞の樹立に成功して以来,疾患特異的iPS細胞の研究が進められてきた.病態発生過程をin vitroで再現できる疾患特異的iPS細胞は,新たな疾患モデルとして病態解明や創薬のための利用が期待される.疾患特異的iPS細胞は心疾患モデルとしても多数樹立されてきたが,これまでは主に遺伝性の不整脈性疾患や心筋症から樹立されており,形態異常を伴う先天性心疾患からは樹立されてこなかった.最近,我々は左心低形成症候群(hypoplastic left heart syndrome: HLHS)由来の疾患特異的iPS細胞の樹立に成功した.遺伝子異常のみならず,遺伝子発現の低下やエピジェネティック制御の異常など,多数の因子が複雑に関与すると考えられる先天性心疾患の病態解明にも,疾患特異的iPS細胞は有用である可能性がある.本総説では,疾患特異的iPS細胞を用いた心疾患モデルの経緯を概説し,また疾患特異的iPS細胞による先天性心疾患の病態解明への可能性を検討する.

Since induced pluripotent stem (iPS) cells have been generated in 2007 from human somatic cells, many studies of disease-specific iPS cells have been reported. Because disease-specific iPS cells can recapitulate disease phenotypes, they are expected to be a novel research tool for in vitro disease modeling to dissect pathogenesis and assist in drug discovery. In terms of cardiovascular diseases, most of the iPS cells have been generated from the patients with inherited arrhythmias or cardiomyopathy. There have been few reports of human iPS cells established from the patients with congenital heart diseases composed of abnormal structures. Most congenital heart diseases are considered to be caused by combinatorial repression of transcription factors and/or impaired epigenetic regulation. Recently, we successfully generated iPS cells from the patients with hypoplastic left heart syndrome (HLHS). We showed that these HLHS-specific iPS cells recapitulated pathogenesis and worked as in vitro disease models for investigating the function of transcription factors during the course of cardiac lineage specification. In this review, we provide an overview of cardiac disease-specific iPS cells and discuss possible uses for dissecting the underlying mechanisms of congenital heart diseases.

Key words: disease-specific iPS cells; congenital heart diseases; differentiation; transcription factors; chromatin remodeling

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This page was last modified on 2015-08-13T10:09:09.228+09:00


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