In Vivo Differentiation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

被引：45

作者：

Yu, Tao ^{[1
,2
]}

Miyagawa, Shigeru ^{[1
]}

Miki, Kenji ^{[1
]}

Saito, Atsuhiro ^{[3
]}

Fukushima, Satsuki ^{[1
]}

Higuchi, Takahiro ^{[1
]}

Kawamura, Masashi ^{[1
]}

Kawamura, Takuji ^{[1
]}

Ito, Emiko ^{[1
]}

Kawaguchi, Naomasa ^{[2
]}

Sawa, Yoshiki ^{[1
]}

Matsuura, Nariaki ^{[2
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Surg, Div Cardiovasc Surg, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Med & Hlth Sci, Dept Mol Pathol, Suita, Osaka 5650871, Japan

[3] Osaka Univ Hosp, Med Ctr Translat Res, Suita, Osaka, Japan

来源：

CIRCULATION JOURNAL | 2013年 / 77卷 / 05期

关键词：

Adhesion molecules; Cardiomyocyte differentiation; Cytoskeleton; Induced pluripotent stem cells; Ultrastructure; CYCLICAL MECHANICAL STRETCH; HEART; REGENERATION; EXPRESSION; THERAPY; MOUSE; HYPERTROPHY; GENERATION; PLASTICITY; VITRO;

D O I：

10.1253/circj.CJ-12-0977

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Induced pluripotent stem cells (iPSCs) hold promise for a new era in treating heart failure. However, the functional microstructure of iPSC-derived cardiomyocytes (iPSC-CMs) and their ability to attach to the extracellular matrix of the recipient myocardium require further elucidation. Thus, we analyzed the functional microstructure and adhesion molecules of iPSC-CM. Methods and Results: Immunostaining analysis showed that iPSC-CMs were similar to neonatal cardiomyocytes (CMs) in expressing the cytoskeletal proteins myosin heavy chain (MHC), myosin light chain (MLC) 2a, MLC2v, and especially beta-mHC (a neonatal CM marker), as well as the adhesion molecules N-cadherin, alpha 7-integrin, dystrophin, alpha-dystroglycan, alpha-sarcoglycan, and laminin-alpha 2. Electron microscopy showed abundant myofibrillar bundles with transverse Z-bands and a developed mitochondrial structure in both iPSC-CMs and neonatal CMs, although the iPSC-CMs contained fewer mitochondria with lower-density cristae. When transplanted from in vitro conditions to nude rat hearts, iPSC-CMs acquired the ability to express alpha-MHC, a molecule specific to adult CMs. Mechanical stretch or stimulation by insulin-like growth factor-1 enhanced the alpha-MHC expression in iPSC-CMs in vitro. Conclusions: Our findings in vitro and in vivo indicate that CMs derived from iPSCs contain cardiac-specific organelles and adhesion systems. These results indicate that iPSC-derived CMs may be useful in new cell therapies for heart failure. (Circ J 2013; 77: 1297-1306)

引用

页码：1297 / 1306

页数：10

共 36 条

[21] MicroRNA-27a Regulates Beta Cardiac Myosin Heavy Chain Gene Expression by Targeting Thyroid Hormone Receptor β1 in Neonatal Rat Ventricular Myocytes [J].