Engineered three-dimensional cardiac tissues maturing in a rotating wall vessel bioreactor remodel diseased hearts in rats with myocardial infarction

被引:12
|
作者
Nakazato, Taro [1 ]
Kawamura, Takuji [1 ]
Uemura, Toshimasa [2 ,3 ]
Liu, Li [1 ]
Li, Junjun [1 ]
Sasai, Masao [1 ]
Harada, Akima [1 ]
Ito, Emiko [1 ]
Iseoka, Hiroko [1 ]
Toda, Koichi [1 ]
Sawa, Yoshiki [1 ]
Miyagawa, Shigeru [1 ]
机构
[1] Osaka Univ, Dept Cardiovasc Surg, Grad Sch Med, Suita, Osaka, Japan
[2] Osaka Univ, Dept Precise & Sci Technol, Grad Sch Engn, Suita, Osaka, Japan
[3] JTEC Corp, Cell Culture Mkt & Res Ctr, Ibaraki, Osaka, Japan
来源
STEM CELL REPORTS | 2022年 / 17卷 / 05期
关键词
CELL-DERIVED CARDIOMYOCYTES; FUNCTIONAL MATURATION; DYNAMIC CULTURE; SHEETS; SURVIVAL; CONTRACTION; ACTIVATION; ADHESION; MUSCLE; FORCE;
D O I
10.1016/j.stemcr.2022.03.012
中图分类号
Q813 [细胞工程];
学科分类号
摘要
A rotating wall vessel (RWV) bioreactor was constructed for growing massive functional cardiac constructs to recover the function of a distressed rat heart. Three-dimensional cardiac tissues were engineered by seeding human-induced pluripotent stem cell-derived cardiomyocytes on poly(lactic-co-glycolic acid) fiber sheets (3D-hiPSC-CTs) and cultured in the RWV bioreactor (RWV group) or under static conditions (control group). The tissues were transplanted into a myocardial infarction nude rat model, and cardiac performance was evaluated. In the RWV group, cell viability and contractile and electrical properties significantly improved, mature cardiomyocytes were observed, and mechanical stress-related mediators of mammalian target of rapamycin signaling were upregulated compared with those of the control. Four weeks post-transplantation, tissue survival and left ventricular ejection fraction significantly improved in the RWV group. Hence, dynamic culture in an RWV bioreactor could provide a superior culture environment for improved performance of 3DhiPSC-CTs, providing a means for functional cardiomyogenesis in myocyte-loss heart failure.
引用
收藏
页码:1170 / 1182
页数:13
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