Engineered Early Embryonic Cardiac Tissue Increases Cardiomyocyte Proliferation by Cyclic Mechanical Stretch via p38-MAP Kinase Phosphorylation

被引:33
作者
Clause, Kelly C. [1 ,2 ]
Tinney, Joseph P. [1 ,3 ]
Liu, Li J. [1 ,3 ]
Keller, Bradley B. [1 ,2 ,3 ]
Tobita, Kimimasa [1 ,2 ,3 ]
机构
[1] UPMC, Childrens Hosp Pittsburgh, Cardiovasc Dev Res Program, Pittsburgh, PA USA
[2] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA
[3] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA
关键词
ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAYS; STEM-CELL TRANSPLANTATION; MUSCLE DIFFERENTIATION; INCREASED PRESSURE; FETAL SHEEP; HEART; P38; AKT; EXPRESSION;
D O I
10.1089/ten.tea.2008.0169
中图分类号
Q813 [细胞工程];
学科分类号
100113 [医学细胞生物学];
摘要
Cardiomyocyte (CM) transplantation is one therapeutic option for cardiac repair. Studies suggest that fetal CMs display the best cell type for cardiac repair, which can finitely proliferate, integrate with injured host myocardium, and restore cardiac function. We have recently developed an engineered early embryonic cardiac tissue (EEECT) using embryonic cardiac cells and have shown that EEECT contractile properties and cellular proliferative response to cyclic mechanical stretch stimulation mimic developing fetal myocardium. However, it remains unknown whether cyclic mechanical stretch-mediated high cellular proliferation activity within EEECT reflects CM or non-CM population. Studies have shown that p38-mitogen-activated protein kinase (p38MAPK) plays an important role in both cyclic mechanical stretch stimulation and cellular proliferation. Therefore, in the present study, we tested the hypothesis that cyclic mechanical stretch (0.5 Hz, 5% strain for 48 h) specifically increases EEECT CM proliferation mediated by p38MAPK activity. Cyclic mechanical stretch increased CM, but not non-CM, proliferation and increased p38MAPK phosphorylation. Treatment of EEECT with the p38MAPK inhibitor, SB202190, reduced CM proliferation. The negative CM proliferation effects of SB202190 were not reversed by concurrent stretch stimulation. Results suggest that immature CM proliferation within EEECT can be positively regulated by mechanical stretch and negatively regulated by p38MAPK inhibition.
引用
收藏
页码:1373 / 1380
页数:8
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